UsTooAdvancedProstateCancer

Prostate Cancer Support Group - Richmond, Va

Meeting Dates - 3rd Thurs. each month - Time 7:00 PM - No July Meeting - The Dec. date will vary - Call for details - Peter C. Moon Phd. at 804-387-2151 between 7 - 11:00 PM - Location - Ridge Baptist Church, 1515 Eastridge Road Richmond, VA 23229

Vet

Rva Prostate Cancer Support Group

www.rvaprostatecancersupport.org

RVA

Advanced Prostate Cancer Page

In good faith, this website was created to furnish you with helpful information. Nevertheless, no one who contributes or posts information to this website makes any guarantee regarding the information provided. Any decisions that you make regarding your health should be made in consultation with a qualified healthcare provider.

Affiliated with Us-TOO International Prostate Cancer Education & Support Network

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Facts and Stats

Emerging Treatments

Complementary
Alternative Treatment Sources

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Advanced Prostate Cancer

Prostate Cancer
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Pluvicto was tested in a clinic trial without having Docetaxel or ADT or may be only limit ADT first

Us Too Warriors,

If you are older(age?) and/or have health issues that make taking Docetaxel difficult your Doctor can get an exception for you to get it like my Brother (87 next week). I think if you are in your late 70's or 80's you should be able to get it or if you have disabilities from the cancer. You may have to hunt to find the Doctor to do it?

(IT appears this trial has been completed. If it has GOOD results reported I hope soon it will make getting Pluvicto easier.)

Best
Peter

Link 1 : "Pluvicto"
or Go To
https://healthunlocked.com/advanced-prostate-cancer/posts/150499765/psma-addition-trial-can-give-access-to-pluvicto-for-denovo-or-mhspc
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Treatment Intensification in Advanced Prostate Cancer" on VuMedi

Us Too Warriors,

The forwarded email below from Dr Moul of Duke University and others that follow deal with recent developments of treatment intensification for men with Advanced PCa.

You can cycle thru the videos to find ones that may help you decide about treatments that fit your situation.
Best
Peter

Dear Peter Moon,
I would like to share with you a video I’ve posted on VuMedi:

"Treatment Intensification in Advanced Prostate Cancer".

Best regards,

Judd Moul, MD
Duke Cancer Institute, Duke University, Durham, NC

Link 1 : "Treatment Intensification in Advanced Prostate Cancer"
or Go To
https://www.vumedi.com/video/treatment-intensification-in-advanced-prostate-cancer/?token=6d7e2b1e-debe-45ce-9853-20114effdb68&utm_source=USERS%20Urology%20ALL_125055&utm_medium=Video&utm_campaign=Treatment%20Intensification%20in%20Advanced%20Prostate%20Cancer&utm_content=Treatment%20Intensification%20in%20Advanced%20Prostate%20Cancer&utm_term=Advanced%20Stage%20Prostate%20Cancer&link_data=eyJidWxrX21haWxfYWN0aW9uIjoiYyIsInJlY2lwaWVudF9pZCI6MTk5ODkyNDA0MiwibWFpbF9pZCI6MTI1MDU1fQ%3A1rSyPQ%3A6KFENkp1ZrifPELO6mtvqIu_IuA5h-WoUPrbkz5M7dU&mail_id=125055
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Cigna Insurance STINKS as they will not pay for PET Scans for advanced cancer

Us Too Warriors,

If you have advanced prostate cancer with rising or Metastasis, You need a pet scan to find its extent so you can treat it best.

Cigna's rules do not allow pet scans and also if you need the latest FDA treatment you have to have a pet scan to show you have PSMA on the surface of your cancer cells to qualify for the Lu177 treatment. So if you have Prostate cancer you need to check your insurance rules to see what imaging your insurance will pay for. If you can not find (Image) your cancer you can not treat it.

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New Treatment for PCa in the works called "Protacs" - looks to have wide application - in phase 2 studies

Us Too Warriors,

This treatment may help many with advanced PCa - I hope it is available Soon and meets its promise.

Best Peter

OUTLOOK - 14 September 2022

The destructive power of PROTACs could tackle prostate cancer
Drugs that direct the body’s proteolytic capabilities towards cancer cells might overcome problems of treatment resistance.

Best
Peter

To See More - Go to the Website - Click on the Link Below:

Link 1 : "Website"
or Go To
https://www.nature.com/collections/ebebjdddab

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Us Too Warriors,
Websites to contact to get reduced cost for Prostate cancer drugs

Us Too Warriors,
The price of PCa drugs can be out of sight without insurance and prohibitive with some insurances.
I am fortunate that my casodex treatment is off patent and considered passe so it only costs me $21 for 3 months(3 pills per day). But my oldest brother, if he did not have good insurance when treated by Dr. Meyers, would have paid $300,000 per year for Xtandi + lupron. He is now on Casodex (psa doubling every 5 months as mine did when it stopped working for me) and I am trying to get his children to Make My Nano Niclosamide treatment for him which cost about $250 for a year of the niclosamide (2grams/day), 75 cents a day for a pint 9.5 pH of water and 35 cents for thirty-five ml of Avocado oil ( for a total ~$650 per year plus a 1/2 hour per day to make).
But I have found a source of websites to contact to ask for reduction in cost for the New drugs that have replaced Casodex and others if you qualify?. See Below.
Best
Peter

To See the Blog - Click on the Link Below:

Link 1 : "Reduced Cost"
or Go To
http://rvaprostatecancersupport.org/PDF/5 30 22 Prostate cancer drugs.pdf
Us Too Warriors,
Mid-Atlantic Clinical trials using CAR-T for castration resistant PCa

Us Too Warriors,
if you have advanced disease this may be of interest. Clinical Trials - See below
Best
Peter

To See the Blog - Click on the Link Below:

Link 1 : "Clinical Trials"
or Go To
http://rvaprostatecancersupport.org/PDF/5 28 22 PSCA.pdf

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Us Too Warriors,
New Nuclear Pet Scan called "PYLARIFY" now available at Henrico Doctors Hospital (Forest)

Us Too Warriors,
Your Doctor needs to set up an appointment for you at this Hospital by calling 804-327-8702 if your PSA is going up after primary treatment. I had previously sent out to you information about this imaging at Sentara hospital in Williamsburg but this site will be closer therefore more convenient for you - it is only five minutes from my house. The copied information from Urology Times discusses the difference in the variety of Pet scan imaging treatments for your benefit.
Best
Peter

To See the Blog - Click on the Link Below:

Link 1 : "PYLARIFY"
or Go To
http://rvaprostatecancersupport.org/PDF/5 5 22 PSMA 2.pdf

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Us Too Warriors,
Anemia in Men With Advanced Prostate Cancer: Incidence, Etiology, and Treatment

Us Too Warriors,
My older brother has had PCa for 29 years and recently his Iron level was Measured at 6% saturation in his transferrin molecules. He recently went to the emergency room because he had chest pains which can be caused by low Iron causing the heart muscles not to get enough oxygen so they are painful. ( He was not having a heart attack). Normal IRON is between 30 and 40 % saturation. I am 24 % saturated recently when I am usually between 30 to 40% saturated. Coffee and Tea drinking will sequester iron out of the body and Citrus or vitamin C pills help increase iron absorption from food like meats etc.
Best
Peter

Abstract:
Anemia associated with advanced prostate cancer is a common occurrence. This article reviews the incidence and examines the various causes of this condition, including androgen deprivation, nutritional decline, bone marrow infiltration, treatment-related toxicity, and the chronic inflammatory state. Treatment of anemia in men with advanced prostate cancer is also discussed. In patients with limited bone marrow reserve, blood transfusions may be the only effective treatment. [Rev Urol. 2004;6(1):1-4]

To read the Info - Click on the Links Below:

Link 1 : "Anemia"
or Go To
http://rvaprostatecancersupport.org/PDF/4 27 22 Anemia.pdf

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Us Too Warriors,
Research showing Salmon may prevent PCa growth from iron in the blood

Us Too Warriors,
I am having salmon for lunch & my cat, Jesica, likes it too.
PS I will be taking my 150mg of Casodex with it.
Best
Peter

To read the Info - Click on the Links Below:

Link 1 : "Salmon"
or Go To
http://rvaprostatecancersupport.org/PDF/4 24 22 Salmon Protein Hydrolysate.pdf

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Us Too Warriors,
Use of radiosensitizers with SBRT

Us Too Warriors,
Jerry and all, I thought you might be interested in this Blog on ways that may make Radiation treatment more effective.

Best
Peter

To read the Blog - Click on the Link Below:

Link 1 : "Radiosensitizers"
or Go To
http://rvaprostatecancersupport.org/PDF/4 11 22 Radiosensitizers.pdf

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Us Too Warriors,
Bipolar Androgen Therapy and the Immune System
Part Three: The Potential of Combination Therapy

Us Too Warriors,

The paper below describes research at John Hopkins that shows that increasing testosterone may benefit a group of men to fight PCa. I am going to talk to my oncologist about doing it for me, but I suspect I will have to go to John Hopkins for the treatment or another University center like in Seattle or S.Carolina or New orleans with well known PCa oncologists.

Best
Peter

Some men are exceptional responders to Bipolar Androgen Therapy (BAT). Its pioneer, medical oncologist Samuel Denmeade, M.D., Co-Director of the Johns Hopkins Prostate Cancer Program, has a few patients who have remained on BAT alone for several years. But for many men, the response is temporary; just a few months. Why? Could it have something to do with mutated genes? What about the immune system?

To see the Article - Click on the Link Below:

Link 1 : "Part Three"
or Go To
https://www.pcf.org/c/bipolar-androgen-therapy-and-the-immune-system/

More Matereial - Supraphysiologic Testosterone Induces Ferroptosis and
Activates Immune Pathways through Nucleophagy in Prostate Cancer

Link 2 : "Supraphysiologic Testosterone"
or Go To
http://rvaprostatecancersupport.org/PDF/2 28 22 Kumar-2021-Supraphysiological-testosterone-ind.pdf

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Us Too Warriors,
Melatonin can block bone met pathways for PCa

Us Too Warriors,

I have taken melatonin for many years - Usually 40 mg to 60 mg per night and if I wake in the night - I will take 20 mg to get back to sleep. I had a bone met in my right hip in Dec 2017 before going on Casodex with dutasteride. I have not had any pain in the hip or sign of a Met there???

Best
Peter

To see the Posts - Click on the Link Below:

Link 1 : "Melatonin"
or Go To
http://rvaprostatecancersupport.org/PDF/2 26 22 Melatonin.pdf

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Us Too Warriors,
Daralutamide and Survival in Metastatic, Hormone Sensitive Prostate Cancer

Us Too Warriors,

I have been a fan of Duralutamide the latest testosterone Receptor blocker on prostate cancer cells and would like to use it as a monotherapy without ADT as I am presently doing with Casodex an early testosterone Receptor blocker on the cancer . The only way to get Daralutamide as a monotherapy, I have heard of, is to get the Duralutamide, is to get and take the Duralutamide pills and get ADT in the newest version as a pill ( Spelled something like Orv,,,,,,y) and not take these ADT pills. I have only heard of one person doing this and have not heard the results, but my Casodex monotherapy reduced my PSA by 99.9% and stopped my hip metastasis started 4 years ago. Casodex ability started to wain after 2 1/2 and now though still using it I am adding a new trick using solubilized Niclosamide that is supposed to according to research to restore Casodex's and Xtandi's punch and this new self made treatment has been working stopping the PSA doubling time of 5months and reducing the PSA by 10% over a four month period of treatment. I hope to disclose the process in a meeting in April or May as Covid I pray continues to wain.

The paper attached below shows the benefit of Duralutamide when used with ADT (which is a bad actor with such problems as weight gain, loss of mobility, muscle strength,, decreased brain function and increased heart failure among others) my oldest brother on Xtandi and ADT has experienced some of them (after being on it for about four years before dropping it). I have been able to reverse/slow his psa rise over the last three years with several off label supplements/treatments. He had Prostate surgery 29 years ago- so he is a trooper. He is on Casodex monotherapy (150mg/d) and dutasteride 0.5 mg/day now like me.
Best
Peter

Abstract
BACKGROUND
Darolutamide is a potent androgen-receptor inhibitor that has been associated with increased overall survival among patients with nonmetastatic, castration-resistant prostate cancer. Whether a combination of darolutamide, androgen-deprivation therapy, and docetaxel would increase survival among patients with metastatic, hormone-sensitive prostate cancer is unknown.

To see the Information - Click on the Link Below:

Link 1 : "Darolutamide"
or Go To
https://healthunlocked.com/advanced-prostate-cancer/posts/147627062/daralutamide-and-survival-in-metastatic-hormone-sensitive-prostate-cancer

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Us Too Warriors,
Dexamethasone is better for use with Zytiga then or after Prednisone for PCa survival

Us Too Warriors,

Objective:
To evaluate the effects of switching from prednisone (P) to dexamethasone (D) at asymptomatic prostate-specific antigen (PSA) progression in patients with metastatic castrationresistant prostate cancer (mCRPC) treated with abiraterone acetate (AA).

Best
Peter

To see the Info - Click on the Link Below:

Link 2 : "Dexamethasone"
or Go To
http://rvaprostatecancersupport.org/PDF/2 21 22 BJU International.pdf

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Us Too Warriors,
Use of Prolactin blocker drug to "CURE" ADT refractory PCa
Us Too Warriors,

This is the first "cure" for cancer at this stage (ADT resistant) I have seen. If you are on ADT you may find this exciting. I have been using a low dose of Cabergoline for years as recommended by Dr. Snuffy Meyers even though I am not on ADT.

See Below - Best For the New Year
Peter

Conclusions:

This report of a novel chemotherapy for androgen-independent malignancy corroborates our understanding of the implications of prolactin in its development and treatment. There are about 165,000 cases/year with 25,000 deaths/year in the U.S.; and 1.0 million cases/year with 260,000 deaths/year worldwide. Those patients with androgen-independent prostate cancer can now employ this cabergoline treatment to prevent or terminate this deadly type of prostate cancer.

To see the Info - Click on the Link Below:

Link 1 : "CURE"
or Go To
http://rvaprostatecancersupport.org/PDF/12 27 21 nihms.pdf

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Us Too Warriors,
blog on " PSA rising on BAT" ==> Replies suggest how to treat it

Us Too Warriors,
This blog discusses how to do BAT treatment and by controlling DHT to keep PSA from rising by using Avodart block DHT but you have to start your Avodart at aPCA below <1.0 mine was 0.29 because I did my research as soon as the PSA came back at 5 years after surgery. If the PSA is above >1.0 when you start Avodart,

It may be slowed for a year or two before it starts growing more rapidly. I was able to use Avodart after cancer returned after surgery to control my PSA rise after surgery for 13 years. In Dec 1999, PSA = 0.29 and in Dec.2013

PSA =1.2 and Dec. 2014 PSA =2.2 . So it started to grow more rapidly and by Dec. 2017 my PSA had risen to12.2 and an Axumin scan showed mets in my right hip bone and multiple pelvic lymph >6 nodes. One of the things you need to know about Avodart is it reduces PSA put out by half so my cancer cells in December 2017 at 12.2 was actually = to a cancer mass = 24.4 PSA so it was not surprising I had metastasis. My reading of the literature is you can have mets show up with PSA in the mid teen range. see more info about Avodart use with BAT treatment.

See below.
Best
Peter

To see the Info - Click on the Link Below:

Link 1 : "BAT"
or Go To
http://rvaprostatecancersupport.org/PDF/11 12 21 PSA rising on BAT.pdf

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Us Too Warriors,
Prostate Cancer treated with ADT Damages 21/2 more failures of the Kidneys and Antiandrogen therapy add is even worse.

Us Too Warriors,
(Link 1)This report is old (2013 ) but news to me. As we age our kidneys work less well as determined by GFR blood test - If you are in the 70 to 80yrs age range if your GFR is in the 70 to 80 ( units?) range, you are doing okay.but when you get down to 30 (units?) in your GFR you are in stage 3 kidney failure.
and
(Link 2)As many of you know I have been using Casodex for ~ 4 years to lower my PSa to undetectable for 3 of those years.

But the attached paper raises some concern about kidney function problems to the extent that the paper suggests adding testosterone to the treatment which is unusual as often casodex is used with ADT which lowers testosterone (an may not recover off of Antiandrogens like casodex etc) and does lead to kidney failure as in the last paper I sent earlier today. However, Casodex blocks testosterone from getting into cells particularly cancer cells so adding testosterone is unusual but may be necessary if you have low testosterone?

I am unusual in that I have very high testosterone ( I have never been on ADT) at 850 to 1500 units. So my kidneys have been OK with a GFR of 70 units at 81 yrs.. But if you have been on ADT or naturally have lower testosterone <450 units you may need to take some amount of testosterone to protect your kidneys as they need it to function well and if you have low kidney function testosterone may help. My Brother has low T after being on Xtandi and lupron (ADT), so he may need to talk to his Doctor about getting some testosterone patches or Injections to protect his kidneys.

This opens the questions about the effects of other Antiandrogens (besides casodex)like Xtandi, Apalutamide, Nubecqa etc on kidneys) especially when used with ADT & low testosterone Men?

See below.
Best
Peter

To see the Info - Click on the Link Below:

Link 1 : "ADT Damages"
or Go To
http://rvaprostatecancersupport.org/PDF/10 31 21 ADT Damages.pdf

Link 2 : "ADT Damages 2"
or Go To
http://rvaprostatecancersupport.org/PDF/10 31 21 ADT Damages 2.pdf

Us Too Warriors,
Book Chapter titled "Key Genes in Prostate Cancer Progression: Role of MDM2, PTEN, and TMPRSS2-ERG Fusions

Us Too Warriors,
The book chapter attached will apply to many men with advanced PCa. Read it carefully to see if it applied to you, I know it applies to me and my brothers with TMRPSS@-ERG fusion genes and it tells me that I and they are not likely to respond to Taxane and docetaxel and as I read elsewhere to Cisplatin treatments which I will be glad to avoid if need as they are not promising for us brothers. There is some information about the p53 gene also. See below.
Best
Peter

To see the Info - Click on the Link Below:

Link : "Key Genes"
or Go To
http://rvaprostatecancersupport.org/PDF/10 8 21 Key Genes.pdf

Us Too Warriors,
Monotherapy of Xtandi has positve results without the use of ADT

Us Too Warriors,
Us of ADT adds to the side effects of Anti Androgen treatment - the side effects of Xtandi and ADT were so bad ( trouble walking, fatigue and mental lapses) that my brother stopped treatment even though it was working after 4 years as prescribed by Dr Meyers. As his PSA climbed off treatment I had him use nitric oxide Snap supplement to help his muscles with walking which helped his muscles but also lowered his PSA by more than 50% for about 8 months. It (PSA) then climbed again so I gave him some of my Casdex ( 2 pills/day instead of my 3 per day) as a monotherapy and his psa is down more than 80% after 2 months. He is trying to find a Doctor in Seattle to give him Casodex as a monotherapy now we have proved it works.

But I have found a paper reporting Xtandi works as a monotherapy works see website to follow but I am concerned he will feel the fatigue and muscle loss he had before (casodex monotherapy has few side effects) so I am trying to find support for Nubequa Mono therapy ( to get a doctor to prescribe it) because it has very few side effects compared to Xtandi or Apalutamide. see website below
Best
Peter

To see the Info - Click on the Link Below:

Link : "Xtandi"
or Go To
https://ascopost.com/issues/july-25-2013/enzalutamide-monotherapy-highly-active-in-patients-with-prostate-cancer-who-have-had-no-prior-hormone-therapy/

Us Too Warriors,
TMPRSS2

Us Too Warriors,
The attached paper is very complex but it suggests that This gene fusion may make Covid more dangerous. TMPRSS2 is one of the means by which Covid gets into our cells to damage them and being Fused to ERG does not seem to help the issue as best I read the paper. I have gotten the booster shot as has one of my brothers and I hope my other brother will too
Best
Peter

To see the Info - Click on the Link Below:

Link : "TMPRSS2"
or Go To
http://rvaprostatecancersupport.org/PDF/9 6 21 main (3).pdf

and

Chemotherapy does not look promising for me or my brothers. You can check to see if you have this gene fusion - if you need too. See attached paper.

Link : "Docetaxel Resistance"
or Go To
http://rvaprostatecancersupport.org/PDF/9 8 21 TMPRSS2.pdf

Us Too Warriors,
Tomatoes

Us Too Warriors,
I hope you have been taking advantage of cooking tomatoes this summer because cooking them helps release them from their skin where Lycopene is found and adding some olive oil to the dish will help release it. I am into making my own cancer medicine which is lipidfilic which allows me to dissolve the active drug into olive oil which I also add 40 mg of lycopene released from their capsules by cutting them open. I will know in three weeks if it is working when I get my next PSA test to see if it has dropped or the rate of climb has stalled (presently doubling every 3 months). The paper below describes the advantage of Lycopene in Prostate , Stomach and lung cancers among others.
Best
Peter

To see the Info - Click on the Link Below:

Link : "Tomatoes"
or Go To
http://rvaprostatecancersupport.org/PDF/8 30 21 Giovannucci-1999-Tomatoes.pdf

and

Potential inhibitory effect of lycopene on prostate cancer
Studying prostate cancer is important due to its high annual incidences and mortality rates in the world. Although prostate cancer mortality rates are reduced using new therapy, complicated routes and side effects of these current drugs require a daily available treatment for prevention. Lycopene is a natural, prominent, and effective product which has a high value in diet. The anti-cancer effect, non-toxicity, safety and preventive or therapeutic roles of lycopene have been investigated in several studies. In the current review, we have collected information about the anti-cancer, anti-progressive and apoptotic effects of lycopene on prostate cancer. This article is a summary of the most important original and review articles on lycopene and its anticancer effects that are systematically categorized and presents information about the molecular structure, different sources, biological functions, and its in-vivo and in-vitro effects of lycopene on variety of cancerous and normal cells. The clinical studies provide a clear image for continuous use of this adjunctive dietary for different type of cancers, especially prostate cancer in men. In addition, this article discusses the various molecular pathways activated by lycopene that eventually prevent or suppress cancer. Lycopene has been found to effectively suppress the progression and proliferation, arrest in-cell cycle, and induce apoptosis of prostate cancer cells in both in-vivo and invitro conditions. Additionally, lycopene showed that it could modulate the signaling pathways and their protein for the treatment or prevention of prostate cancer

Link : "lycopene"
or Go To
http://rvaprostatecancersupport.org/PDF/9 1 21 Mirahmadi-2020-Potential-inhibitory-effect-of-lyco.pdf

Us Too Warriors,
Blog on Honokiol benefit for P53 mutated PCa

I have been taking Magnolia bark as a source of Honokiol from Swanson. The blog that follows suggests HonoPure from ECO Nutrients which I am going to investigate. Read below for more information.

Best
Peter

To see the Info - Click on the Link Below:

Link : "Honokiol"
or Go To
http://rvaprostatecancersupport.org/PDF/7 26 21 HONOKIOL.pdf

Us Too Warriors,
Lu177 treatment success and failure Blog

It helps some men with Advanced cancer, but it also can cause the cancer to take off for others. It may not be an easy decision to know if you are a good candidate?? Pten Mutation ( a very bad actor) in your cancer makes you a bad candidate For Lu177.

One of our members with Pten mutation went to Germany for Lu 177 treatment about 2017 and he succumbed to to his cancer within a year in 2018 waiting for a new clinic trial.

Best
Peter

To see the Info - Click on the Link Below:

Link : "Lu177"
or Go To
http://rvaprostatecancersupport.org/PDF/7 26 21 LU177.pdf

Us Too Warriors,
Niclosamine and Indomethacin May make Anti-androgens like Casodex, Enzalutamide work after they start to fail do to AV-7

This is a treatment I am investigating as my casodex is starting to fail after 3 years. I will start it within a month and may know how it is working by the fall. See abstract and patent that follow. Wish me well and I hope it can help others in our group.
Abstract:

Enzalutamide and Indomethacin in Treating Patients with Recurrent or Metastatic Castration-Resistant Prostate Cancer

This phase I / II trial studies the side effects of enzalutamide and indomethacin and to see how well they work in treating patients with prostate cancer that does not respond to treatment with hormones despite surgical removal of testes (castration-resistant), has come back (recurrent), or has spread from where it started to other places in the body (metastatic). Androgens can cause the growth of prostate cancer cells. Indomethacin is a non-steroidal anti- inflammatory drug that has been found to block one of the signals that enhance prostate cancer cell growth. Hormone therapy using enzalutamide and indomethacin may fight prostate cancer by lowering the amount of androgen the body makes and / or blocking the use of androgen by the tumor cells.

Location: University of California Davis Comprehensive Cancer Center, Sacramento.

Best
Peter

To see the Info - Click on the Link Below:

Link : "Patent"
or Go To
http://rvaprostatecancersupport.org/PDF/7 12 21 Patent Application.pdf

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Us Too Warriors,
Selective androgen receptor modulators- SARMs look very promising as new PCa treatment -available without a prescription

This SARMs use for PCa is new to me as of today and it has been Clinically tested at U. of Washington. I am ordering some online to try today.

It is used by weight lifters and is good to build muscle, fat loss and bone health as well as prevent muscle wasting (cachexia) from cancer.

It has positive benefits for these conditions as opposed to these negative conditions produced by Lupron ADT.

Best
Peter

To see the Info - Click on the Link Below:

Link : "SARMs"
or Go To
http://rvaprostatecancersupport.org/PDF/6 18 21 SARM.pdf

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Us Too Warriors,
PSMA imaging test now availble in Fort Lauderdale

This test recently approved for imaging advanced cancer. See below.

Best
Peter

To see the Info - Click on the Link Below:

Link : "Pylarify"
or Go To
http://rvaprostatecancersupport.org/PDF/6 18 21 Pylarify.pdf

Us Too Warriors,
New Australian Drug for very Advanced PCa w/ SBRT radiation or
Lu177 increases Median Survival from 5 to 20 months!!

Check Out this website for Information and it may be in clinical trials in the USA?

Best
Peter

To see the Blog - Click on the Link Below:

Link : "Survival"
or Go To
https://www.outsourcing-pharma.com/Article/2021/03/02/Prostate-cancer-treatment-shows-major-survival-benefit

Us Too Warriors,
Aplutamide with ADT for men with more aggresive PCa responded better than men with less agressive PCa

It is hard to know the outcome of a treatment until it is tested or you try it. So there is hope it can work for you. See the paper attached below

Best
Peter

To see the Info - Click on the Link Below:

Link : "Aplutamide"
or Go To
http://rvaprostatecancersupport.org/PDF/6 4 21 jamaoncology_feng_2021_oi_210018_1621868087.01914-1.pdf"

Us Too Warriors,
Paper comparing 2nd & 3rd level Antiandrogens Apalutamide, Enzalutamide, and Darolutamide Clinicla trials nmCastration resistant PCa

The paper attached below describes the side effects found in the Clinical trials and the effectiveness in treating nmCastration resistant PCa.

My brother had to stop Enzalutamide as the fatigue was so great it interfered with his mobility/walking. This fatigue problem was also pointed out by the clinical trial. He is trying a short course of Casodex as monotherapy, a level 1 antiandrogen, that has worked for me going on 3 1/2 years. If and when Casodex fails for me I would consider Darolutamide as it has the best side effect profile except Afib. See the attached paper to inform yourself.

Best
Peter

To Go to the Website - Click on the Link Below:

Link : "Antiandrogens"
or Go To
http://rvaprostatecancersupport.org/PDF/6 3 21 s41391-020-00310-3.pdf"

Us Too Warriors,
My Personal "trial" of Cyclic Testosterone Therapy

This blog describes a brave man who has blazed a path for others by working with his Doctors. It is early in the game but the results look very promising. This is not BAT=Bipolar Androgen therapy because no ADT is Used. It should be called " Monopolar Testosterone therapy".

Best
Peter

To Go to the Information - Click on the Link Below:

Link : "Cyclic"
or Go To
http://rvaprostatecancersupport.org/PDF/5 20 21 My Personal.pdf

Us Too Warriors,
Clinical trials for LU 177 PMSA for hormone sensitive PCa- most in the USA

Check out this website if you have advanced PCa.

Now that the VISION trial of Lu-177-PSMA-617 is no longer recruiting, some patients are wondering if they can still get PSMA-targeted radiopharmaceuticals in the US, without traveling to Germany, Australia, India, etc. Here is a list of trials that are active, still open to recruitment, or will soon be recruiting.
Best
Peter

To Go to the Website - Click on the Link Below:

Link : "Clinical Trial"
or Go To
https://www.prostatecancer.news/2020/08/psma-targeted-radiopharmaceutical.html
***********************************************
Us Too Warriors,
Blog on Bat

I have not figured them out as each person has a different cancer.

But It looks like it can make Casodex last longer and can also make enzalutamide be reactivated after CRPC in some men.
Best
Peter

(Both Links below are on the same Blog - Different Threads)

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From the Blog:

G’day comrades

I have tried to report my experiences with Bipolar Androgen Therapy (BAT). You will find them in my profile.

This will be the last as the anti androgen I use (bicalutamide) failed in spectacular fashion. I will post on subsequent treatments. The pattern of failure may interest. Hist: Failure of long running ADT (zoladex) was about 2015 when I started bicaulutamide. It failed after 12 months and I decided that was a good time to see what my reaction to BAT might be. All experiences differ but all information is potentially useful. If you have a doc who will prescribe it, then it is a very simple intramuscular injection once a month. You can easily learn to do it yourself (google it).

To Go to The Blog - Click on the Link Below:

Link 1 : "Blog"
or Go To
https://healthunlocked.com/advanced-prostate-cancer/posts/145582729/end-of-bat-a-few-lessons

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This looks like this is a good treatment for advanced PCa especially for men who have failed different "alutamide" Drugs to make them work again. which will grow as we learn better how to manage it for different men's conditions. E2 skyrockets on BAT therapy
Best
Peter

To Go to The Blog - Click on the Link Below:

Link 2: "Bat"
or Go To
https://healthunlocked.com/advanced-prostate-cancer/posts/146123113/e2-skyrockets-on-bat-therapy
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Us Too Warriors,
"Wormwood" from Swanson is my Source of Artemisinin

See the attached paper on Artemisinin. I also got some Artemisinin seeds to plant when it is warmer (research discovery of Artemisinin and its benefits won a Noble prize in 2015). Best
Peter

To Read The Paper - Click on the Link Below:

Link : "Artemisinin"
or Go To
http://rvaprostatecancersupport.org/PDF/2 23 21 molecules-21-01331.pdf
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Us Too Warriors,
Paper attached on ways to make P53 negative PCa more able to responded chemotherapy

The paper below looks like it could be helpful.

Best
Peter

To Read The Paper - Click on the Link Below:

Link : "Paper"
or Go To
http://rvaprostatecancersupport.org/PDF/2 23 21 aging-12-103377-1.pdf
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Us Too Warriors,
Beginning of a break thru in Advanced cancer P13K_AKT_mTOR pathways

It has been hard to crack the CODE to stop advanced cancer with P53 or/And P10 Mutations.

We have one member who responded to Rapamycin while having multiple bone mets which treats mTOR pathway which has an mTOR1 and mTOR2 paths that both have to be blocked which worked for him in a John Hopkins Clinical Trial to put him in remission. But he was one of the few to respond. It appears that if you have mutations in P53 or/and P10 you may need to block most or All the P13K_AKT_mTOR pathways. The attached paper discusses the research to try to accomplish this Goal to extend life.

Best
Peter

To Read The Paper - Click on the Link Below:

Link : "Pathways"
or Go To
https://www.urotoday.com/clinical-trials/from-the-editor/126829-pi3k-akt-mtor-inhibitors-for-prostate-cancer-finally-hints-of-a-breakthrough.html#:~:text=PI3K/AKT/mTOR%20Inhibitors%20for%20Prostate%20Cancer%20%E2%80%93%20Finally%20Hints,castration-resistant%20prostate%20cancer.%201,2%20Not%20surprising%20is

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Us Too Warriors,
Statin treatments for Advanced PCa have improved survival

It appears that from the attached paper below that the Lipophilic statin = Pitavastatin is the most effective in preventing PCa deaths and the second best is the Hydrophilic Statin = Pravastatin. I got my GP doctor to prescribe Pravastatin about a year ago as my LDL was higher than it had been. It is now lower, but I may talk to him about Pitavastatin as it is significantly better for PCa survival.

The website below is another paper about statins but it does not have much on pitastatin as there were not many men using it. Best
Peter

To Read The Paper - Click on the Link Below:

Link : "Statin"
or Go To
http://rvaprostatecancersupport.org/PDF/2 21 21 Wu-2019-Mortality-associated-with-statins-i.pdf

To go to the Website - Click on the Link Below:

Link : "Website"
or Go To
https://www.cancernetwork.com/view/statins-associated-lower-all-cause-and-prostate-cancer-mortality
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Us Too Warriors,
Advances in the Treatment of Metastatic Prostate Cancer

Workshop Date and Time

Tuesday, February 23, 2021, 1:30 – 2:30 pm, Eastern Time - Register Now

Registrants can listen in live over the phone or online as a webcast.

Some of The Topics Covered

Overview of the Treatment of Metastatic Prostate Cancer in the Context of COVID-19 -- Advances in the Treatment of Metastatic Prostate Cancer
Updates on the Treatment & Care of Bone Metastases -- The Role of Chemotherapy, Radiation Oncology & Targeted Treatments
The Importance of Clinical Trials, in the Context of COVID-19 -- How Clinical Trials Contribute to Your Treatment Options
The Role of Precision Medicine

Sign up for the conference at Website Link Below.
Best
Peter

To Read Register - Click on the Link Below:

Link 1 : "Website Link"
or Go To
https://www.cancercare.org/connect_workshops/864-advances_in_the_treatment_of_metastatic_prostate_cancer_2021-02-23

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Us Too Warriors,
Nutrition and Cancer

See attached paper below.

Best
Peter

ABSTRACT

Nutrition and Cancer

While each person and each cancer diagnosis is unique, general guidance before, during and after treatment includes eating nutritious foods to help focus on healthy habits. When you are healthy, eating enough food may not be a problem. But when you are dealing with cancer and treatment, this may be harder to do. Chemotherapy, surgery, radiation therapy and other cancer treatments may take a toll on the body. They may affect taste, smell, appetite, how much food is eaten and the ability to absorb nutrients from food. This cookbook is designed to help you think about what you eat and to help you select meals while you or someone you love is dealing with cancer. Talk with your physician or care team about cancer treatment, as well as about what to eat during cancer treatment. They may refer you to a dietitian who can help you with your diet and to choose foods and drinks during and after treatment.

To Read the Book - Click on the Link Below:

Link : "Cookbook"
or Go To
http://rvaprostatecancersupport.org/PDF/1 22 21 PP-XDI-USA-0219Living Healthy Cookbook with Information about Urologic Cancers-1.pdf
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Us Too Warriors,

Therapeutic Potential of Leelamine, a Novel Inhibitor of Androgen Receptor and Castration-Resistant Prostate Cancer

See the link below for more information.

Best Holiday
Peter

Abstract:

Clinical management of castration-resistant prostate cancer (CRPC) resulting from androgen deprivation therapy remains challenging. CRPC is driven by aberrant activation of androgen receptor (AR) through mechanisms ranging from its amplification, mutation, post-translational modification, and expression of splice variants (e.g., AR-V7). Herein, we present experimental evidence for therapeutic vulnerability of CRPC to a novel phytochemical,leelamine (LLM), derived from pine tree bark. Exposure of human prostate cancer cell lines LNCaP (an androgen-responsive cell line with mutant AR), C4-2B (an androgen-insensitive variant of LNCaP), and 22Rv1 (a CRPC cell line with expression of AR-Vs), and a murine prostate cancer cell line Myc-CaP to plasma achievable concentrations of LLM resulted in ligand-dependent (LNCaP) and ligand-independent (22Rv1) growth inhibition in vitro that was accompanied by downregulation of mRNA and/or protein levels of full-length AR as well as its splice variants including AR-V7. LLM treatment resulted in apoptosis induction in the absence and presence of R1881. In silico modelling followed by luciferase reporter assay revealed a critical role for non-covalent interaction of LLM with Y739 in AR activity inhibition. Substitution of the amine group with an isothiocyanate functional moiety abolished AR and cell viability inhibition by LLM. Administration of LLM resulted in 22Rv1 xenograft growth suppression that was statistically insignificant but was associated with a significant decrease in Ki-67 expression, mitotic activity, expression of full-length AR and AR-V7 proteins, and secretion of prostate-specific antigen. The present study identifies a novel chemical scaffold for the treatment of CRPC.

More Info - Click on the Link Below:

Link: "Leelamine"
or Go To
http://rvaprostatecancersupport.org/PDF/1 1 21 Singh-2018-Therapeutic-potential-of-leelamine-.pdf
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Us Too Warriors,

Turmeric in Combination with Quercetin

One of the ways PCa progresses on ADT or on Androgen receptor blocking Mono Therapy like Casodex or in combined ADT and Xtandi is by the cancer increasing the number of Androgen receptors (This is caused making a bigger Sail so even low Testosterone grows the cancer).

I have recently read that testosterone in Turmeric in combination with quercetin helps to block this process. I have started to have some growth in my Casodex monotherapy so I added more Turmeric and Quercetin to my treatments to stop the growth.

Best Holiday
Peter

Abstract:

Cancer is a hyperproliferative disorder that is usually treated by chemotherapeutic agents that are toxic not only to tumor cells but also to normal cells, so these agents produce major side effects. In addition, these agents are highly expensive and thus not affordable for most. Moreover, such agents cannot be used for cancer prevention. Traditional medicines are generally free of the deleterious side effects and usually inexpensive. Curcumin, a component of turmeric (Curcuma longa), is one such agent that is safe, affordable, and efficacious. How curcumin kills tumor cells is the focus of this review. We show that curcumin modulates growth of tumor cells through regulation of multiple cell signaling pathways including cell proliferation pathway (cyclin D1, c-myc), cell survival pathway (Bcl-2, Bcl-xL, cFLIP, XIAP, c-IAP1), caspase activation pathway (caspase-8, 3, 9), tumor suppressor pathway (p53, p21) death receptor pathway (DR4, DR5), mitochondrial pathways, and protein kinase pathway (JNK, Akt, and AMPK). How curcumin selectively kills tumor cells, and not normal cells, is also described in detail.

More Info - Click on the Link Below:

Link: "Combination"
or Go To
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2758121/
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Us Too Warriors,

Neem

Neem is my Latest addition to help my PCa Fight

Best Holiday
Peter

NEEM/AND ITS COMPONENTS AS EFFECTIVE AGENTS FOR PREVENTION, TREATMENT AND CELL DEATH, FOR PCA, AND OTHER CANCERS.

The 2 main components of Neem that are active against cancer, are Azadirachtin, and Nimbolia. I am doing below my research summarization. And for those that want to study these compounds and Neem can find lots to read in Pub Med, Science Direct et. al. and I do not copy and paste.

Usually Ethanolic extracts of Indian Neem Leaf are what are used in the study of the effects on cancer cell lines. Yes Prostate included. Natives of India have use the Neem Leaf for 400 years, and the local Herbalists, over many decades regularly treat cervical cancer with Neem Preparations.

More Info - Click on the Links Below:

Link 1: "Neem"
or Go To
https://healthunlocked.com/advanced-prostate-cancer/posts/144946771/neem-and-its-components-as-effective-agents-for-prevention-treatment-and-cell-death-for-pca-and-other-cancers.#post-responses
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Link 2: "Gov-Link Neem"
or Go To
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6682706/
*
Link 3: " Sloan Kettering Cancer Center-Link Neem"
or Go To
https://www.mskcc.org/cancer-care/integrative-medicine/herbs/neem
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Us Too Warriors,

FDA Puts RV001 on Fast Track for Treating Prostate Cancer

FDA fast tracks a vaccine treatment to block Metastasis. See below and attachment of Paper reporting results of clinic trial.

The U.S. Food and Drug Administration (FDA) has granted fast track status to RV001, RhoVac's investigational therapy for prostate cancer, the company announced. Fast track designation helps speed the approval of potential medicines that address unmet medical needs in serious or life-threatening conditions. It grants RhoVac greater access to FDA input throughout the regulatory process and makes RV001 eligible for accelerated approval and priority review, if it meets certain criteria. With the fast track designation, RhoVac also may apply for a "rolling review," in which the company submits sections of its biologic license application for review as they are completed, rather than all together after clinical testing finishes. "We are extremely pleased and proud that our drug candidate, RV001, has earned fast track designation by the FDA," Anders Månsson, RhoVac's CEO, said in a press release. "The fact that the FDA has reviewed our data, and found our drug candidate worthy of this level of priority ... sends a clear signal of recognition of the drug's potential to all our would-be partners, which is something of great importance to us," Månsson said. RV001 is a peptide-based medicine meant to prevent cancer recurrence and spread. The treatment mimics the Ras homolog gene family member C (RhoC), a protein that helps cancer cells migrate and take hold in other tissues, and stimulates the immune system to recognize and target cells producing this protein. While these treatments historically have shown poor effectiveness against solid tumors, the goal of RV001 is to target the metastatic cancer cells, rather than the solid primary tumor. In this manner, the treatment is expected to eliminate spreading cells before they establish hard-to-treat tumors outside the prostate.
Best
Peter

More Info - Click on the Links Below:

Link: "RV001"
or Go To
https://prostatecancernewstoday.com/2020/12/08/fda-puts-rv001-on-fast-track-for-treating-prostate-cancer/
*
Link: "Trial Info"
or Go To
https://www.clinicaltrials.gov/ct2/show/record/NCT04114825?term=RV001&cond=Prostate+cancer&cntry=US&draw=2&rank=1

Us Too Warriors,

Key Genes in Prostate Cancer Progression:

This book chapter below may help you use and Understand your Gene analysis to help you control your cancer.

For example, with my TMPRSS2-ERG Mutation, my cancer is very responsive to lowering Dihydrotestosterone with Avodart/proscar and blocking the Androgen receptors with Casodex, and I read that inflammation with NF-Kb pathway pushes TMPRSS2-ERG mutated patients to have Mutations so their PTen gene (which is protective when working- not mutated) becomes mutated (inactive). This helps explain why I have been helped by Avodart, Proscar and recently by Casodex to block testosterone and I think my years of taking multiple anti-inflammatories over the years has keeped me from developing a mutation in my Pten gene which is a Killer,

Best
Peter

Key Genes in Prostate Cancer Progression: Role of MDM2, PTEN, and TMPRSS2-ERG Fusions

Abstract:

In recent years, multiple genes or their protein products have been linked to initiation and progression of prostate cancer. Such genes include TMPRSS2, ERG, PTEN, and MDM2. This chapter discusses the pathological roles as well as the potential diagnos‐ tic and therapeutic applications of these genes that are highly expressed in prostate cancer when compared to other cancer types. The presence of these genes and related defects are linked to growth, progression, metastasis, invasiveness and resistance in prostate cancers. While knowledge related to TMPRSS2, ERG, and PTEN have been accumulating in the last two decades, the prometastatic role of MDM2 has been emerging in the last few years and revealing important functions related to prostate cancer progression.

More Info - Click on the Link Below:

Link: "Key"
or Go To
http://rvaprostatecancersupport.org/PDF/12 7 20 51830 (1).pdf

Us Too Warriors,

"“Fluciclovine (18F) PET/CT Impact on Clinical Management of Recurrent Prostate Cancer”

I hope all are well and celebrate a health Thanksgiving. The video attached below is by Dr. Androile who recommended Finasteride (1996) and the Avodart later to stop Dihydrotestosterone fuel PCa growth after BCR - this along with my supplements gave me 15 years of slow PSA growth after I experienced BCR in Year 2000. It is the Axumin test for BCR which he discusses in the video that helped find my Mets which so far Casodex has lowered my PSA which is considered undetectable by standard PSA test.

I think this Video will help you decide at what PSA values after BCR to get an Axumin test. It is more successful as the PSA rises. My PSa was 12.2 ng/ml when I could first get the test after FDA approval ( it is highly effective for detection at this PSA). It is a much better test lymph node mets than mpMRI imaging. MY MRI at that time detected no lymph node mets but Axumin found about 8 lymph node mets in addition to hip bone met. My MRI did not find the hip bone met initially but it did when a new MRI, after the Axumin, was extended to cover my Hips. I did not know the original MRI(s) 2 only looked at the pelvis ( If you do not look in the right place you will not find Mets). I hope this helps

Fluciclovine (18F) PET/CT Impact on Clinical Management of Recurrent Prostate Cancer
Gerald L. Andriole, MD, FACS, asserts that the fluciclovine PET-CT scan has a significant impact on the management of patients with biochemically recurrent prostate cancer. Best
Peter

Summary: Gerald L. Andriole, MD, FACS, asserts that the fluciclovine PET-CT scan has a significant impact on the management of patients with biochemically recurrent prostate cancer. Prostate cancer recurs in up to 40% of patients treated with surgery or radiation therapy for presumed localized disease. Unfortunately, conventional imaging is unlikely to identify the site of recurrence until the Prostate Specific Antigen (PSA) level exceeds 20 mg/mL. Choline PET scans are an improvement over conventional imaging but are not recommended until the PSA level exceeds 20 mg/mL.

Fluciclovine PET scans identify recurrence disease in about 40% of patients with PSA levels less than 0.8 mg/mL, but identifies higher portions of patients as PSA levels rise. In a treatment impact trial of more than 200 men with biochemically recurrent prostate cancer (the LOCATE study), treatment was changed in 59% of patients once the results of the fluciclovine PET scan were known. In 78% of these cases, the treatment changes were considered to be major.

To See the Video - Click on the Link Below:

Link: "Fluciclovine"
or Go To
https://grandroundsinurology.com/fluciclovine-18f-pet-ct-impact-on-clinical-management-of-recurrent-prostate-cancer/

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Us Too Warriors,

Fight Multiple Cancers

This is a possible path to fight multiple cancers including PCa which I am investigating. See Attachments.
See below for information

Best
Peter

Fenbendazole acts as a moderate microtubule destabilizing agent and causes cancer cell death by modulating multiple cellular pathways :

Benzimidazoles Downregulate Mdm2 and MdmX and Activate p53 in MdmX Overexpressing Tumor Cells

Click on the Links Below:

Link: "Benzimidazoles"
or Go To
http://rvaprostatecancersupport.org/PDF/11 12 20 Benzimidazoles.pdf
*
Link: "Fenbendazole"
or Go To
http://rvaprostatecancersupport.org/PDF/11 12 20 Fenbendazole.pdf

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Us Too Warriors,

Natural Products ( Flavanoids $ Drugs) that inhibit Covid and PCa from binding energies by computer molecular modeling calculations

The attached Papers suggest natural products that may bind to TMPRSS2 protease proteins to fight Covid and PCa. I had projects in dentistry about bone mineralization using molecular modeling about 25 years ago so I know it is very complex. The simplified way to look at it is:"the more negative the sum of all the binding energies among the natural products and TMPRSS2; the stronger the bond so that it (the bound natural product molecules) will interfere with TMPRSS2, stopping the Covid virus from entering our cells or the growth of PCa. These natural molecules found in food or supplements (Neohesperidin, Myricitrin, Quercitrin, Naringin, Icariin, and Ambroxol) were found to work against the TMPRSS2 protein in the paper . You will have to search for these supplements as I will to find sources.

These following drugs also block TMPRSS2 proteins by binding to them; Camostat, Bromhexine and Guaifenesin. Camostat is used in Japan for pancreatitis. Bromhexane is available overseas in cough medicines as I discussed in another recent email. Guaifenesin is found in American over-the- counter Cough/Mucus relieving medicines (Easiest to get at a drugstore). Do not use any cold/cough medicine that contains DM==>Dextromethorphan which is bad for prostate ( cancer/ enlargement). These cough relief agents release TMPRSS2 from our throat and chest so they can be spit out to excrete them form body so the can do not harm.See below for the paper.
Best
Peter

To See the paper below:

Click on the 3 Links:
Link 1 "Covid"
or Go To
http://rvaprostatecancersupport.org/PDF/10 27 20 PCa-TMPRSS2 natural product inhibitors for PCa and Covid.pdf
*

Link 2 "Anti-TMPRSS2"
or Go To
http://rvaprostatecancersupport.org/PDF/10 27 20 tbsd_a_1798813_sm6268.pdf
*

Link 3 "Natural Poducts"
or Go To
https://www.tandfonline.com/doi/pdf/10.1080/07391102.2020.1798813?needAccess=true&
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Us Too Warriors,

The Androgen-Regulated Protease TMPRSS2

This is an over the counter used in tablets and Cough syrups available in many countries overseas - not in the USA. It rids the throat and lungs of TMPRSS2 proteins that initiate Covid damage there. It also suppresses PCa growth by blocking TMPRSS2-ERG growth promoting PCa Mutation formation by reducing TMPRSS2 proteins. This may be beneficial for covid and PCa but if you have liver or Lung issues you will need to be careful to limit the amount used and check these organs with blood tests to cause no harm.

The Androgen-Regulated Protease TMPRSS2 Activates a Proteolytic Cascade Involving Components of the Tumor Microenvironment and Promotes Prostate Cancer Metastasis
Best
Peter

To See the paper below:

Click on the Link:
"Therapeutic Implications"
or Go To
http://rvaprostatecancersupport.org/PDF/10 27 20 Lucas-2014.pdf
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Us Too Warriors,

Metastasis

The research website below suggest that men as they progress to Metastasis may develop this mutation and be less responsive to Chemo.

TMPRSS2-ERG in Blood and Docetaxel Resistance in Metastatic Castration-resistant Prostate Cancer

See website below for more information.

Best
Peter

To See the Website below:

Click on the Link:
"Metastasis"
or Go To
https://pubmed.ncbi.nlm.nih.gov/26948395/
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Us Too Warriors,

FoTi

I have been taking Emodin = FoTi = Pterostilbene for about 14 years. I talked to Dr. Meyers about them in 2008 he warned me about taking them so I tripled down and took more. He had studied them and thought them a poison . I reasoned that they might poison my cancer. Here I am in remission still taking them for 14+ years later.
You decide for yourself.

Best
Peter

See paper attached below.
To see the Paper:
Click on the Link:
"FoTi"
or Go To
http://rvaprostatecancersupport.org/PDF/10 10 20 Lin-2012-Activation-of-ampk-by-pterostilbene.pdf
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Us Too Warriors,

Androgen deprivation Therapy (ADT for PCa) and low testosterone may Increase chances of Kidney damage

My last brother diagnosed (Oct2019) with PCa has reduced Kidney Function and lower levels of testosterone so I thought I should see if there could be a connection between low testosterone and Kidney function.

The two papers attached below show there can be an increased problem with kidney function with low testosterone natural and by use of ADT. So if you have either of these conditions you need to check your Kidney function with CBC blood tests to see if it is affecting your kidneys by looking at your GFR levels and your Creatinine level.

Best Peter
*
To Read The Papers:

Click on the Links:

Link 1 : "Link 1"
or Go To
http://rvaprostatecancersupport.org/PDF/9 25 20 David-Testosterone Replacement Therapy (TRT) is Associated better Kidney function in Veterans.pdf *

To Read More Local Information:

Click on the Link:

Link 2 : "Link 2"
or Go To
http://rvaprostatecancersupport.org/PDF/9 25 20 joi130032.pdf
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Us Too Warriors,

Optimal chemohormonal sequencing for mCRPC MAY be Taxotere->Zytiga->Jevtana->Xtandi

(1) Taxotere (docetaxel) first

In a retrospective study presented at the Society for Urologic Oncology meeting, researchers at the Mayo Clinic reported on 112 patients with metastatic castration-resistant prostate cancer (mCRPC).

•Group A (80 men) had docetaxel (Taxotere) followed by one of the second-line hormonal therapies: either abiraterone (Zytiga) or enzalutamide (Xtandi)
•Group B (32 men) had a second-line hormonal therapy followed by Taxotere.
•Bone metastases were more common in Group B (87%) than Group A (58%)

Best Peter

To Read More:

Click on the Link:

Link: "Optimal Chemohormonal"
or Go To
https://www.prostatecancer.news/2019/12/optimal-chemohormonal-sequencing-for.html

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Us Too Warriors,

Testosterone Therapy in Men with Advanced Prostate Cancer

I think you know by now I use Metformin, Avodart/proscar, Doxycycline & Casodex with many anti-oxidanta+antiflammatories to fight my cancer so far successfully without fatigue for my TMPRSS2-ERG Mutation PCa which occurs in my family. My Brother was on ADT (Lupron) with Xtandi that had produced fatigue to the point he had trouble walking without cane and had fatigue so he stopped them 9+ months ago and his PSA went up from .078 to 6.8 a doubling rate of less than 2 months. He is trying to see a Doctor out in U of Washington that does BAT ( BIPOLAR Androgen(Lupron then Testosterone) therapy. The Youtube video below discusses many aspects of high dose testosterone treatment which you will find enlightening and shocking to learn high testosterone treatment was prevented when only one man had a poor outcome in the 1940's when Hudgins reported this among the 3 men treated.

See Video below especially if you are on Lupron or your Doctor talks to you about it.

Best Peter

To Read the blog:

Click on the Link:

Link: "Testosterone Therapy"
or Go To
https://www.youtube.com/watch?time_continue=1&v=wafNZV-Hkqk&feature=emb_logo

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Us Too Warriors,

Erleada without ADT

Find below information on Casodex in place of ADT(Lupron) you may find useful.
Best Peter

You will have to create a login to vciew posts.

To Read More:

Click on the Link:

Link : "Casodex"
or Go To
https://healthunlocked.com/advanced-prostate-cancer/posts/144329819/erleada-without-adt?uid=a13a9e99-aa40-4a58-bdb5-a2b5e68984b5&utm_campaign=advanced-prostate-cancer&utm_medium=email&utm_source=notification&utm_term=new-daily+digest#post-responses
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Us Too Warriors,

High dose testosterone causes DNA damage and suppresses prostate cancer growth

I am very excited about this trial and my oldest Brother is in Seattle Wa. I do not know all the details yet, But I would like them to include Avodart to prevent high levels of Dihydrotestosterone which could drive Covid damage. OR use after we have a Vaccine for Covid.

Best Peter

To Read More:

Click on the Link:

Link: "Testosterone"
or Go To
https://cdmrp.army.mil/pcrp/research_highlights/20schweizer_highlight

*
Us Too Warriors,

Radiation and Immunotherapy

Dr Drake is one of Jerry Deans Docs in NY,NY.

This paper makes interesting points of How Radiation and Immunotherapy may work together to make a local radiation treatment have a systemic effect.

Best Peter

To Read More:

Click on the Link:

Link: "Radiation and Immunotherapy"
or Go To
https://grandroundsinurology.com/radiation-immunotherapy-the-abscopal-effect/

***********************************************
Us Too Warriors,

Attachments

I hope you find something useful in the Attachments. The first attachment describes a phase 3 trial designed which will open in the 4 th quarter which is for advanced cancer that has failed Xtandi or Zytiga with rising PSA. The second attachment has many other topics that may be helpful. All the Best

Best Peter

To Read More:

Click on the Link:

Link: "4 th Quarter"
or Go To
https://www.onclive.com/view/fda-provides-regulatory-clarity-on-phase-3-trial-design-for-veru-111-in-mcrpc

*

Link: "Other Topics"
or Go To
https://www.prostatepedia.net/blogs/prostatepedia

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Us Too Warriors,

Cryosurgical Tumor Cell Lysis and Intratumoral Immunotherapy

Regression of metastatic cancer and abscopal effects following in situ vaccination by cryosurgical tumor cell lysis and intratumoral immunotherapy: A case series

Abstract:

Purpose: To evaluate the efficacy and safety of a novel in situ cancer vaccination method for the treatment of aggressive solid tumors, with an initial focus on metastatic prostate cancer (PCa). Procedure: 27 consecutive patients with metastatic cancers (21 with PCa and 6 with other cancers), were treated by in situ cryosurgical lysis of tumor tissue followed by injection of ipilimumab, pembrolizumab or nivolumab, and sargramostim directly into the zone of lysis. This was followed by 30 daily s.c. injections of sargramostim. Patients received 1 to 3 cycles of the above therapy at intervals of ≥ 1 month. Responses to therapy were assessed by RECIST v.1.1 and for patients with PCa, serum PSA levels. This IRB-approved study, Shulman IRB Protocol #00027107, is a retrospective analysis (with prospective follow-up) of the practice of medicine of two physicians. All patients signed informed consent. Results: 21 patients with progressive metastatic PCa and 6 with other metastatic cancers (2 bladder, 1 pancreatic, 1 colon, 1 melanoma, and 1 unknown) were treated. RECIST responses for 2 patients (both with PCa) could not be evaluated due to a lack of follow-up imaging. Among the remaining 25 patients, CRs were seen in 9 (36%) patients and a PR in 1 (4%), for an ORR of 40%. SD was seen in 8 (32%) patients, and progression was seen in 7 (28%).
Best Peter

To Read More:

Click on the Link:

Link: "Immunotherapy "
or Go To
https://www.abstractsonline.com/pp8/#!/9045/presentation/7023

*
Us Too Warriors,

Curcumin and Turmeric

Natural products targeting the p53-MDM2 pathway and mutant p53: Recent advances and implications in cancer medicine

Abstract:

The p53 tumor suppressor plays a major role in controlling the initiation and development of cancer by regulating cell cycle arrest, apoptosis, senescence, and DNA repair. The MDM2 oncogene is a major negative regulator of p53 that inhibits the activity of p53 and reduces its protein stability. MDM2, p53, and the p53-MDM2 pathway represent welldocumented targets for preventing and/or treating cancer. Natural products, especially those from medicinal and food plants, are a rich source for the discovery and development of novel therapeutic and preventive agents against human cancers. Many natural product-derived MDM2 inhibitors have shown potent efficacy against various human cancers. In contrast to synthetic small-molecule MDM2 inhibitors, the majority of which have been designed to inhibit MDM2- p53 binding and activate p53, many natural product inhibitors directly decrease MDM2 expression and/or MDM2 stability, exerting their anticancer activity in both p53-dependent and p53- independent manners. More recently, several natural products have been reported to target mutant p53 in cancer. Therefore, identification of natural products targeting MDM2, mutant p53, and the p53-MDM2 pathway can provide a promising strategy for the development of novel cancer chemopreventive and chemotherapeutic agents. In this review, we focus our discussion on the recent advances in the discovery and development of anticancer natural products that target the p53-MDM2 pathway, emphasizing several emerging issues, such as the efficacy, mechanism of action, and specificity of these natural products.
Best Peter

To Read More:

Click on the Link:

Link: "Curcumin and Turmeric"
or Go To
http://rvaprostatecancersupport.org/PDF/07 27 20 PCa-Natural products targeting the p53-MDM2 in PCa.pdf

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Us Too Warriors,

Dr. Bilusic (he spoke at one of our meetings) of NIH - Casodex and Metformin Clinic trial

This is the main treatment that put my cancer in remission. I also take doxycycline and avodart/+proscar along with many antioxidants and anti- inflammatories. This treatment works particularly well for men who have the TMPRSS2-ERG fusion mutation which may occur 50% or more PCa men.

My brothers have the same germline mutation I do. Chris Maxwell in our group took part in the NIH clinical study and had a lowering of his PSA but the study as a whole was not as successful as the selection was restricted and recruiting was difficult. I have been able to make indirect contact with Dr. Kinloch Nelson of Va Urology for Chris to continue the treatment which I hope he will. I think if they had tried it on men with TMPRSS2-erg fusion mutation it would have been very successful. I have also read a paper showing Xtandi is very successful in slowing cancer with mutation growth. Xtandi worked very well for my oldest brother for four years until the fatigue became too much so his PSA is going up now. I am trying to get him to try Casodex Etc which I think will have fewer side effects. The TMPRSS2-ERG mutation is very active in regard to testosterone so at low PSA it reacts well to Avodart and Proscar that keep my cancer growing slowly for 15 years until my PSA grew above 1.0 so by the time it got to 12.2 at 3 years later I had a bone met in my hip and 6+ in my lymph nodes.

Know 2.5 years later my PSA=0.028 and at this level i can not image mets so I am in remission as far as I can tell and my general practitioner is helping me to maintain this treatment as my VCU oncologist retired and and his replacement can not think outside the box of Standard of care Treatment.

If after reading the attachment if you have BCR cancer recurrence and you would like to consider this treatment, especially if you know you have TMPRSS2-ERG Mutation, email me and I will try to contact Dr Nelson in your Behalf to see if it can help you. You do not have to have cancer that fits the parameters of the NIH clinical trial.
Best Peter

To Read More:

Click on the Link:

Link: "Clinic trial"
or Go To
https://www.prostatepedia.net/blogs/prostatepedia/join-a-clinical-trial-casodex-bicalutamide-metformin

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Us Too Warriors,

Apigenin: A Promising Molecule for Cancer Prevention

Abstract Apigenin, a naturally occurring plant flavone, abundantly present in common fruits and vegetables is recognized as a bioactive flavonoid shown to possess anti-inflammatory, antioxidant and anticancer properties. Epidemiologic studies suggest that a diet rich in flavones is related to a decreased risk of certain cancers, particularly cancers of the breast, digestive tract, skin, prostate and certain hematological malignancies. It has been suggested that apigenin may be protective in other diseases that are affected by oxidative process such as cardiovascular and neurological disorders, although more research needs to be conducted in this regard. Human clinical trials examining the effect of supplementation of apigenin on disease prevention have not been conducted although there is considerable potential for apigenin to be developed as a cancer chemopreventive agent.
Best Peter

To Read More:

Click on the Link:

Link: "Apigenin"
or Go To
http://rvaprostatecancersupport.org/PDF/07 19 20 PCa-Apigenin- A Promising Molecule for Cancer Prevention.pdf

Us Too Warriors,

FDA Grants Priority Review to Relugolix for Men With Advanced Prostate Cancer

This will reduce the problems of heart and strokes problems from Lupron. See Below

An oral 120 mg dose of relugolix (Relumina) has received a priority review designation from the FDA for the treatment of patients with advanced prostate cancer, Myovant Sciences announced in a press release. The target FDA action date has been set for December 20, 2020.1

“We are delighted that the FDA has accepted for Priority Review our New Drug Application for relugolix, bringing us one step closer to providing a one pill, once a day potential new treatment option to men with advanced prostate cancer,” said Lynn Seely, MD, chief executive officer, Myovant Sciences. “As recently published in the New England Journal of Medicine, relugolix demonstrated superior efficacy and a 54% lower risk of major adverse cardiovascular events (MACE) compared to the current standard of care, leuprolide acetate injections, in the Phase 3 HERO study.”

Best Peter

To Read More:

Click on the Link:

Link: "Relugolix"
or Go To
https://www.targetedonc.com/view/fda-grants-priority-review-to-relugolix-for-men-with-advanced-prostate-cancer

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Us Too Warriors,

Dr. Meyers Prescription

I thought you might want to revisit Dr. Meyers prescription to see if it has anything to help you control your cancer. it is Attached below:

Best Peter

To Read More:

Click on the Link:

Link: "Dr. Meyers Prescription"
or Go To
https://grandroundsinurology.com/durable-complete-remission-prostate-cancer/

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Us Too Warriors,

This is better for the heart than Lupron - if on ADT.

Oral Relugolix for Androgen-Deprivation Therapy in Advanced Prostate Cancer

Conclusions:
In this trial involving men with advanced prostate cancer, relugolix achieved rapid, sustained suppression of testosterone levels that was superior to that with leuprolide, with a 54% lower risk of major adverse cardiovascular events. (Funded by Myovant Sciences; HERO ClinicalTrials.gov number, NCT03085095.).
Best Peter

To Read More:

Click on the Link:

Link: "Relugolix"
or Go To
https://pubmed.ncbi.nlm.nih.gov/32469183/

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HERO Phase 3 Trial: Relugolix vs. Leuprolide Acetate for Advanced Prostate Cancer –

Summary:

Neal D. Shore, MD, FACS, Medical Director for the Carolina Urologic Research Center, presents the key aspects of the HERO phase 3 trial. The HERO trial looked at Relugolix, an oral GnRH receptor antagonist, versus Leuprolide Acetate for the treatment of advanced prostate cancer. He begins by going over the study design, patient demographics, and clinical characteristics. He then goes over some of the study’s key and secondary endpoints, all of which were met.

To Read More - Click on the Link:

Link: HERO
or Go To
https://grandroundsinurology.com/hero-phase-3-trial-relugolix-vs-leuprolide-acetate-for-advanced-prostate-cancer/

Study reveals a way to make prostate cancer cells run out of energy and die.

Deguelin, an inhibitor of mitochondria in cells, can be used to target lethal prostate cancers lacking the gene PTEN. Left: cancerous mouse prostate cells glow green. Right: After 10 weeks of treatment with deguelin, only a few cancer cells remain. This compound and another called rotenone, kill cells missing PTEN but don't harm normal cells by exploiting cancer cells' dependency on glucose.

To Read More - Click on the Links:

Link: Study
or Go To
https://www.cshl.edu/study-reveals-way-make-prostate-cancer-cells-run-energy-die/
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Us Too Warriors,

I have been using 150mg /day casodex/day, 100 mg of Doxycycline/d, 1500mg of Metformin/d, dostinex 0,5mg/week and Calcitriol 0.5mcg /d (This is the maximum amount of calcitriol I can take on a low calcium intake diet to keep my calcium in my blood in safe range< , 10.8 in my blood). Plus all my many supplements that have put my cancer in remission.
The information that follows is information I found which discusses how Calcitriol reacts favorably with TMPRSS2-ERG Mutations to fight PCa.
For your information:
Best Peter

To Read More - Click on the Links:

Link: Vit D
or Go To
http://rvaprostatecancersupport.org/PDF/04 10 20 Revealing Vitamin D Pathways to Prostate Cancer Prevention and Treatment.pdf

Link: 2 Vit D
or Go To
http://rvaprostatecancersupport.org/PDF/04 10 20 Vit D 17968-262380-4-PB.pdf

Us Too Warriors,

Family and friends, My casodex treatment has raised my Testosterone to 1600 ng/ml blood level.

This video attached suggests that 2000 to 3000 ng/ml is a good level to shoot for so I have added Horny Goat weed, Tribulus, and fenugreek supplements to raise T. I also take avodart and proscar to to lower DHT which also raises my T. I found at age 60 with BCR of the cancer (year =2000) when my T = 475 and DHT = 40 that when I went on proscar my after 3 months my T=525 and DHT < 5. From 2000 to 2013 my PSA <1.0 on proscar, avodart, doxycycline ,dostinex and high dose active vitamin D. Since then in Dec 2017, I had a PSA =12.2 with multiple lymph node mets and bone met in right hip , I added Casodex and metformin Along with 70+ different supplements per day and my PSA = 0.026 Feb 2020. Cancer in remission I think? See video below from John Hopkins and U of Washington on high T treatment.. I found recently that my germline mutation is TMPRSS2-ERG fusion with a high level of ERG production which makes it less favorable. This mutation is a hormone testosterone growth sensitive. This mutation my make one more prone to Pten somatic mutation prone as hinted at in the cancer literature. See the Test results of the Video below as I couldn't figure out how to copy the video for you
Best Peter

To see More - Click on the Link:

Link: Testosterone
or Go To
http://rvaprostatecancersupport.org/PDF/03 28 20 Testosterone Replacement in the Treatment of Advanced Prostate Cancer.pdf

Us Too Warriors,

All, This looks promising for advanced PCa.
Best Peter

Prostate-specific membrane antigen (PSMA)-targeting Radio-Ligand Therapy with beta-emitting 177Lutetium has already been investigated in several early phase dosimetry studies, demonstrated promising results in phase-2, and recently the first phase-3 trial finished recruitment. In contrast, PSMA-targeting alpha-particle therapy (TAT) has only been evaluated in few preclinical experiments, preliminary dosimetry attempts and some retrospective observational studies, yet. First clinical experience with 225Ac-PSMA-617 demonstrates promising antitumor activity with a 63%-70% PSA>50%-response rate, 10-15 months duration of response and complete remissions in approximately ten percent of patients, some of them with enduring relapse-free survival.

For More Information - Click on the Link:

Link: Radio-Ligand Therapy
or Go To
https://www.urotoday.com/recent-abstracts/urologic-oncology/prostate-cancer/120144-225ac-psma-617-for-therapy-of-prostate-cancer.html

Us Too Warriors,

Below are information Changes that may occur as the Pandemic gets worse.
Best Peter

COVID-19 Pandemic Rearranges Oncology Practice, Policies at Seattle Cancer Care Alliance
Danielle Ternyila - Published Online:1:00 PM, Fri March 20, 2020

As the Coronavirus disease 2019 (COVID-19) pandemic evolves, healthcare providers in the oncology realm are faced with a number of unforeseen challenges requiring immediate attention and swift changes in policies. Experts at the Seattle Cancer Care Alliance (SCCA) shared their insights and advice with the public in a recent article to demonstrate how they have adapted to provide the most optimal care for patients with cancer in light of the COVID-19 outbreak.

For More Information - Click on the Link:

Link: Oncology Practice
or Go To
https://www.targetedonc.com/news/covid19-pandemic-rearranges-oncology-practice-policies-at-seattle-cancer-care-alliance?p=1

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Us Too Warriors,

This test is for men with advanced cancer with a rising PSA or CRPC or metastasis. These conditions should make it approvable by insurance if you have a tissue biopsy. If no biopsy, you will have to see what you can negotiate a for blood liquid biopsy test cost with the company. However, the liquid test is being submitted for FDA approval which may come through this year?? So Before you read all the details see if applies to your cancer situation

Websites follow for you to GOOGLE - see the link below

To see More - Click on the Link:

Link: Metastasis
or Go To
http://rvaprostatecancersupport.org/PDF/03 19 20 advanced cancer with rising PSA or CRPC.pdf

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New Principle for Eradicating Cancer: Leave No Dead Cells Behind

Killing cancer cells is the fundamental objective of chemotherapy, radiation and targeted cancer therapies. However, these treatments often fail to eradicate tumors, and cancer often recurs.

So, is killing the problem?

Dr. Dipak Panigrahy at Beth Isreal Deaconess Medical Center in Boston and colleagues at Harvard Medical School, show that dead cells, or cell debris, generated by treatments intended to eradicate tumor cells, actually act as strong stimulators of tumor progression. Their findings were published in The Journal of Experimental Medicine on November 30.

To Read the Article - Click on the Link:

Link: Leave No Dead Cells Behind
or Go To
http://rvaprostatecancersupport.org/PDF/03 06 20 New Principle for Eradicating Cancer.pdf

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Fatigue

RVA - Us Too Warriors:

Fatigue is a common symptom

Fatigue is a common symptom from cancer treatments especially advanced cancers and if on ADT Lupron and some antiandrogens like Xtandi.

Consumer Labs which analyzes supplements for purity and reliability of the dose content also discusses their use to help reduce fatigue. (See below)

To Read the Article - Click on the Link:

Link: Fatigue
or Go To
http://rvaprostatecancersupport.org/PDF/3 4 20 Supplements to Increase Energy.pdf

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Celastrol, an active constituent of the TCM plant Tripterygium
wilfordii Hook.f., inhibits prostate cancer bone metastasis

Background:
Treatment failure of prostate cancer (PCa) is often due to bone metastasis. Celastrol, an active constituent of Tripterygium wilfordii roots, has shown anti-tumor effects in previous studies in accordance with its indication in traditional Chinese medicine.

To Read more on this Subject
Click on the Link:

Link: Celastrol
or Go To
https://www.nature.com/articles/pcan201661

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Anti-androgens may increase mortality risk in men with CVD
Badar M. Mian, MD
August 30, 2019 - Volume: 47 - Issue: 9

Genitourinary Cancers, Prostate Cancer

Badar M. Mian, MDAdvanced prostate cancer and cardiovascular disease often coexist in older men. Over the last 5 years, new second-generation antiandrogens, namely abiraterone (ZYTIGA) and enzalutamide (XTANDI), are being used with more frequency in men with advanced prostate cancer. Patients with significant cardiovascular disease (CVD) are often excluded from clinical trials for reasons that are understandable. But in clinical practice, the excluded patients are often the ones treated with those same medications.

A new study suggests that newer antiandrogens may increase the risk of early mortality and hospitalization, especially in men with known CVD such as myocardial infarction, atrial fibrillation, congestive heart failure, stroke, or ischemic heart disease (Eur Urol Aug. 2, 2019 [Epub ahead of print]).

Lu-Yao and colleagues used the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked files (representing nearly 31% of the U.S. population) to identify men with prostate cancer who had received chemotherapy and abiraterone or enzalutamide. A total of 3,876 patients were eligible for the study, including 2,845 treated with abiraterone and 1,031 treated with enzalutamide. The main goal of the analysis was to determine the mortality rate within 6 months after starting therapy with these two antiandrogens. They also wished to determine the risk of hospitalization after the initiation of antiandrogen therapy.

Also from Dr. Mian: Untreated MIBC has short natural course, significant morbidity

Interestingly, 67% of the eligible patients had one or more documented CVD before receiving abiraterone or enzalutamide.

In the post-chemotherapy group of patients being treated with abiraterone, 24% died within 6 months, compared with 17% in the pivotal trial that led to its approval. Among patients being treated with enzalutamide, 28% died within 6 months, compared with 12% in the pivotal trial. In the group without chemotherapy, 18% of patients died within 6 months of starting abiraterone and 17% died within 6 months of starting enzalutamide.

In the post-chemotherapy cohort receiving either abiraterone or enzalutamide, there was no significant difference in hospitalization rates between the two drugs. However, those with one or two CVDs had a 43% increased risk of hospitalization compared to those with no CVDs.

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Next: Higher hospitalization rate in abi patients with no chemo

Antiandrogens may increase mortality risk in men with CVD: Page 2 of 2
Badar M. Mian, MD

August 30, 2019 - Volume: 47 - Issue: 9

Genitourinary Cancers, Prostate Cancer

Higher hospitalization rate in abi patients with no chemo

In the group without chemotherapy, abiraterone was associated with a higher rate of hospitalization than enzalutamide among patients with one or more CVDs. In this group, hospitalization rate was higher with abiraterone use even in the patients with no history of CVD.

As stated by the authors, the worse outcomes (cardiovascular toxicity and/or mortality) following the use of abiraterone have been reported by previously published meta-analyses. In the STAMPEDE trial, the addition of abiraterone was associated with improved cancer-free-survival but no real improvement in overall survival, likely due to increased cardiovascular mortality.

It appears that abiraterone is associated with worse outcomes even if there is no documented chemotherapy or CVDs. However, without direct comparison, we cannot suggest that one drug is superior to the other. Other antiandrogens such as apalutamide (Erleada) and darolutamide (Nubeqa) have been approved recently and the use of antiandrogens has been moving “upfront;” eg, before chemotherapy and without metastases. This will likely result in increased use of drugs in this class, making the issue of adverse outcomes even more relevant.

Read: Renal mass biopsy safe, but when is it necessary?

The usual limitations of a retrospective analysis apply to this study as well. The data do not allow for a comparison with an appropriate control group that did not receive abiraterone or enzalutamide, or direct comparison. However, the Medicare-linked SEER data represent a broad cross-section of the population that is afflicted with prostate cancer and CVDs, which makes the information presented here quite pertinent for most clinicians.

The phenomenon of worse outcomes in the real-world setting after the initial approval of a drug or device has been well documented. Clinicians often loosen the criteria beyond what was allowed in the clinical trials, exposing the patients to a host of drug-drug or drug-disease interactions.

The subjects of this study had also received androgen deprivation therapy, which is associated with developing CVDs. Is it possible that these subjects were primed, through previous use of ADT, for worse outcomes following the addition of abiraterone and enzalutamide? The unique contribution of these second-generation antiandrogens to cardiovascular mortality is not entirely clear.

Several professional organizations are offering workshops geared towards incorporating these and other oral anti-cancer agents into the practice of urology. Hopefully, the educational activities will sufficiently emphasize a more careful selection of patients for these drugs. There is a clear impetus for a multidisciplinary program to monitor the treatment and adverse outcomes of newer antiandrogens which, at present, may be out of the comfort zone of many urologists.
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Overview of Treatment for Advanced Prostate Cancer, including Metastatic Disease – Novel Treatment – Summary:

RVA - Us Too Warriors:

Abstract:
The genetic landscape of prostate cancer has been well-mapped in recent years, and the discovery of the vast array of mutations that can occur in mCRPC has led many researchers to try and determine if any are actionable. Novel therapies currently in development include androgen receptor inhibitors, epigenetic modulators, cyclin-dependent kinase (CDK) 4/6 inhibitors, and various immunotherapies, but researchers looking at PI3Kinase/Akt inhibition, PARP inhibitors, and Lu-PSMA have presented the most promising data so far.

To Read more on this Subject
Click on the Link:

Link: Novel Therapies
or Go To
https://grandroundsinurology.com/overview-of-treatment-for-advanced-prostate-cancer-including-metastatic-disease-novel-treatment/?utm_campaign=Weekly%20Email%20GRU&utm_source=hs_email&utm_medium=email&utm_content=83375949&_hsenc=p2ANqtz--HeuHAk88-eSaWcZLrTYO7RFwgQyKTXu2YPf9W0IOjar38r52gxIPmBYHVshAjww9GQqtoIawLsgsQFqs42_YzLRzxjw&_hsmi=83375949

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Alternating High Testosterone and Lupron shots

RVA - Us Too Warriors:

The Alternating High Testosterone and Lupron shots in clinical trials are starting to be reported with positive results at John Hopkins and Seattle cancer centers. A video is attached below. It is not recommended if you have clinical pain from advanced PCa cancer in bones, but it looks as if it may stimulate response to immunotherapy treatment!!!!! and PARP inhibitor treatments!!!!

To Watch the Testosterone Replacement in the Treatment of Advanced Prostate Cancer - Sam Denmeade and Michael Schweizer Video
You can also Read the Full Video Transcript.
Click on the Link:

Link: High Testosterone
or Go To
https://www.urotoday.com/video-lectures/prostate-cancer-foundation-2019/video/mediaitem/1594-testosterone-replacement-in-the-treatment-of-advanced-prostate-cancer-sam-denmeade-and-michael-schweizer.html?utm_source=newsletter_7465&utm_medium=email&utm_campaign=prostate-cancer-daily

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Systemic Alkalinisation Delays Prostate Cancer Cell Progression in TRAMP mice

RVA - Us Too Warriors:

IS Alkaline water Good for Bone density, Preventing dental decay, dry mouth from chemo therapy, and slowing Prostate cancer???.

Abstract
The microenvironment of solid tumours is extremely acidic and this condition arises since the precancerous stage. This acidic milieu could therefore provide a useful target for both prophylactic and therapeutic approaches. In TRAMP transgenic mice, an in vivo model of prostate adenocarcinoma (AC), oral administration of alkaline water was devoid of unwanted side effects, and when started from an early age was as effective as NaHCO3 in significantly delaying tumour progression, while when started when prostate tumours were already present, a nonstatistically significant trend in the same direction was detected. These findings indicate that the use of alkalinizing drugs should be considered for chemoprevention and, in association with standard chemotherapy, for treatment of human prostate AC.

To Read the Article - Click on the Link:

Link: Alkalinisation
or Go To
http://rvaprostatecancersupport.org/PDF/2 9 20 Astigiano-2017-Systemic-alkalinisation-delays-pros.pdf

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Quercetin Targets hnRNPA1 to Overcome Enzalutamide Resistance in Prostate Cancer Cells

RVA - Us Too Warriors:

I read that this may keep Taxane from failing too. Dose recommended of quercetin is 1000 to 3000 mg /day.

Abstract
Prostate cancer remains dependent on androgen receptor signaling even after castration. Aberrant androgen receptor signaling in castration-resistant prostate cancer is mediated by mechanisms such as alterations in the androgen receptor and activation of interacting signaling pathways. Clinical evidence confirms that resistance to the next-generation antiandrogen, enzalutamide, may be mediated to a large extent by alternative splicing of the androgen receptor to generate constitutively active splice variants such as AR-V7. The splice variants AR-V7 and ARv567es have been implicated in the resistance to not only enzalutamide, but also to abiraterone and other conventional therapeutics such as taxanes. Numerous studies, including ours, suggest that splicing factors such as hnRNPA1 promote the generation of AR-V7, thus contributing to enzalutamide resistance in prostate cancer cells. In the present study, we discovered that quercetin, a naturally occurring polyphenolic compound, reduces the expression of hnRNPA1, and consequently, that of AR-V7. The suppression of AR-V7 by quercetin resensitizes enzalutamide-resistant prostate cancer cells to treatment with enzalutamide. Our results indicate that quercetin downregulates hnRNPA1 expression, downregulates the expression of AR-V7, antagonizes androgen receptor signaling, and resensitizes enzalutamide-resistant prostate cancer cells to enzalutamide treatment in vivo in mouse xenografts. These findings demonstrate that suppressing the alternative splicing of the androgen receptor may have important implications in overcoming the resistance to next-generation antiandrogen therapy. Mol Cancer Ther; 16(12); 2770–9. ©2017 AACR.
Best Peter

To Read the Article - Click on the Link:

Link: Quercetin
or Go To
https://mct.aacrjournals.org/content/16/12/2770

*****

Reactivation of PTEN tumor suppressor for
cancer treatment through inhibition of a MYC-WWP1 inhibitory pathway

RVA - Us Too Warriors:
Abstract:
Activation of tumor suppressors for the treatment of human cancer has been a long sought, yet elusive, strategy. PTEN is a critical tumor suppressive phosphatase that is active in its dimer configuration at the plasma membrane. Polyubiquitination by the ubiquitin E3 ligase WWP1 (WW domain–containing ubiquitin E3 ligase 1) suppressed the dimerization, membrane recruitment, and function of PTEN. Either genetic ablation or pharmacological inhibition of WWP1 triggered PTEN reactivation and unleashed tumor suppressive activity. WWP1 appears to be a direct MYC (MYC proto-oncogene) target gene and was critical for MYC-driven tumorigenesis. We identified indole-3-carbinol, a compound found in cruciferous vegetables, as a natural and potent WWP1 inhibitor. Thus, our findings unravel a potential therapeutic strategy for cancer prevention and treatment through PTEN reactivation.
Best Peter

To Read the Article - Click on the Link:

Link: Suppressor
or Go To
http://rvaprostatecancersupport.org/2 4 20 PCa-Reactivation of PTEN tumor suppressor REX.pdf

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PSA Doubling Time and Absolute PSA Predict Metastasis-free Survival

RVA - Us Too Warriors:

PSA Doubling Time and Absolute PSA Predict Metastasis-free Survival in Men With Biochemically Recurrent Prostate Cancer after Radical Prostatectomy - Beyond the Abstract
My cancer metastasized between my 16th and 19th years after BCR. During that time My PSA went from 2.2 to 12 and PSA doubling time went from 18 months at the 16th year to 5 months in the 19th year. I wish I had started my present casodex/metformin/avodart(dutasteride)/doxycycline treatment when my PSA started to double faster after it went over 1.3 which had a doubling time of 3 to 4 years. I start the caosodex/etc treatment as soon as the Axumin pet scan showed multiple lymph nodes in my pelvis and in my right hip socket femur. Two MRI scans during this 3 year fast rise in PSA did not show any mets because MRI is not good at seeing lymph node mets and MRI did not extend down to my hip - I did not know these limitations when had 2 MRIs as my PSA increased faster. I did have the MRI extended to cover my hip and the hip bone met showed up.

If possible you should add treatments to stop mets if your PSA is rising fast (a short doubling time the abstract below indicates that a doubling time of less than 7.5 months for is point at which mets will occur. I would suggest 9 months to give you time to get the treatment started. Read the following abstract to get more information. I am fortunate that my METs have respond for two years now with PSA < 0.025 - I do not know if I have no mets now because I can not image them as the PSA is to low to detect

Best Peter

To Read the Article - Click on the Link:

Link: PSA Doubling Time
or Go To
https://www.urotoday.com/recent-abstracts/urologic-oncology/prostate-cancer/118729-psa-doubling-time-and-absolute-psa-predict-metastasis-free-survival-in-men-with-biochemically-recurrent-prostate-cancer-after-radical-prostatectomy-beyond-the-abstract.html

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CRPC produced by ADT treatment of Hormone Sensitive Cancers

RVA - Us Too Warriors:

The attached papers indicated CRPC produced by ADT treatment of hormone sensitive cancers makes the cancer grow by increasing prolactin which can be blocked by drugs that block prolactin, Cabergoline (dostinex) or bromocriptine, to possible put the CRPC cancer in remission.
Best Peter

To Read the Articles - Click on the Links:

Link: Clioquinol
or Go To
http://rvaprostatecancersupport.org/PDF/1 26 20 PCa-Clioquinol.pdf

Link: PCa-prolactin
or Go To
http://rvaprostatecancersupport.org/PDF/1 26 20 PCa-prolactin.pdf

Link: PCa-Termination
or Go To
http://rvaprostatecancersupport.org/PDF/1 26 20 PCa-Termination of Untreatable Androgen-independent Prostate cured with Cabergoline.pdf

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PSMA Targeted Therapies Presentation - Michael Hofman

RVA - Us Too Warriors:

Professor Michael Hofman presented on prostate-specific membrane antigen (PSMA) targeted therapies during the Management of castration-resistant prostate cancer (CRPC) session at the Advanced Prostate Cancer Consensus Conference (APCCC) 2019, presenting data from both of his groups in Australia. Dr. Hofman highlights the progress of a single-centre, single-arm, phase 2 study; [177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer of which in 2015, his group started enrolling. Before concluding, Dr. Hofman highlights several trials with 177Lu-PSMA that are ongoing.

To Watch PSMA Targeted Therapies Presentation - Michael Hofman Video
Click on the Link:

Link: PSMA
or Go To
https://www.urotoday.com/video-lectures/precision-medicine-in-prostate-cancer/video/1467-players-brightcove-net2019-09-10-14-49-08.html

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Initial Experience with Actinium - 225 PSMA in Advanced Prostate Cancer - Machaba Michael Sathekge

Mike Machaba Sathekge, MD, PhD presents on the power of medicine, specifically targeted radionuclide therapies and the use of actinium-225 in advanced prostate cancer. Targeted α-therapy with 225Ac-PSMA-617 although still preliminary, has demonstrated strong potential to significantly benefit advanced-stage prostate cancer patients. He discusses the initial experience with 225Ac-PSMA-617 in a developing country, as one of the first groups to provide this therapy.

To Watch 225 PSMA in Advanced Prostate Cancer Video
Click on the Link:

Link: 225 PSMA
or Go To
https://www.urotoday.com/video-lectures/snmmi-curriculum/video/1606-initial-experience-with-actinium-225-psma-in-advanced-prostate-cancer-machaba-michael-sathekge.html

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Naturally occurring anti-cancer agents targeting EZH2

RVA - Us Too Warriors:

Some of you may be using metformin because of Pre or Diabetes or to reduce your blood sugar to fight PCa. And a few because of NIH clinic study using it with Casodex with metformin which I put you on to and is working for at least four men in our group(including me)! The attachment will show research to develop a drug to block EZH2 growth pathway and natural agents I have been recommending (curcumin and berberine etc) that make metformin more effective in blocking this Pathway.

Abstract:
Natural products are considered as promising tools for the prevention and treatment of cancer. The enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase unit of polycomb repressor complexes such as PRC2 complex that has oncogenic roles through interference with growth and metastatic potential. Several agents targeting EZH2 has been discovered but they often induce side effects in clinical trials. Recently, EZH2 has emerged as a potential target of natural products with documented anti-cancer effects and this discloses a new scenario for the development of EZH2 inhibitory strategies with agents with low cytotoxic detrimental effects. In fact, several natural products such as curcumin, triptolide, ursolic acid, sulforaphane, davidiin, tanshindiols, gambogic acid, berberine and Alcea rosea have been shown to serve as EZH2 modulators. Mechanisms like inhibition of histone H3K4, H3K27 and H3K36 trimethylation, down-regulation of matrix metalloproteinase expression, competitive binding to the S-adenosylmethionine binding site of EZH2 and modulation of tumor-suppressive microRNAs have been demonstrated to mediate the EZH2-inhibitory activity of the mentioned natural products. This review summarizes the pathways that are regulated by various natural products resulting in the suppression of EZH2, and provides a plausible molecular mechanism for the putative anti-cancer effects of these compounds.

Best Peter

To Read the Articles - Click on the Links:

Link: Anti-cancer Agents
or Go To
https://www.sciencedirect.com/science/article/abs/pii/S0304383517301842

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Urologic Surgery and Mechanisms of Therapeutic Resistance

RVA - Us Too Warriors:

Some interesting research follows that you can apply to your fight.

Message from the Director of Research
"We are the one of the largest urologic research programs in the nation with six research laboratories and over $4 million in research grants in 2014."
Allen C. Gao, M.D., Ph.D. - Director of Research -Department of Urologic Surgery
and Suppressing the nuclear receptor protein ROR-?; with small-molecule compounds can reduce androgen receptor (AR) levels in castration-resistant prostate cancer and stop tumor growth.

and

Mechanisms of Therapeutic Resistance in Prostate Cancer

Abstract:
Abstract Prostate cancer is the second leading cause of cancer deaths in the USA. The challenge in managing castration-resistant prostate cancer (CRPC) stems not from the lack of therapeutic options but from the limited duration of clinical and survival benefit offered by treatments in this setting due to primary and acquired resistance. The remarkable molecular heterogeneity and tumor adaptability in advanced prostate cancer necessitate optimization of such treatment strategies. While the future of CRPC management will involve newer targeted therapies in deliberately biomarker-selected patients, interventions using current approaches may exhibit improved clinical benefit if employed in the context of optimal sequencing and combinations. This review outlines our current understanding of mechanisms of therapeutic resistance in progression to and after the development of castration resistance, highlighting targetable and reversible mechanisms of resistance.

Best Peter

To Read the Articles - Click on the Links:

Link: Urologic Surgery
or Go To
http://rvaprostatecancersupport.org/PDF/1 19 20 Message.pdf

To read Mechanisms of Therapeutic Resistance in Prostate Cancer
Click on the Link:

Link: Therapeutic Resistance
or Go To
http://rvaprostatecancersupport.org/PDF/1 19 20 PCa-Mechanisms.pdf

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Treatment Gene Testing

RVA - Us Too Warriors:

I made these comments at the meeting to help men determine at what stages in their treatment gene testing is valuable in planning your treatment . These are my comments

The Attached Video was shown at our Jan 16, 2020 meeting.
Genetics in Prostate Cancer: Identification of Inherited Prostate Cancer Risk –

Summary:
Leonard G. Gomella, MD, FACS, reviews basic concepts of genetics and genomics, the role of genetics and genomics testing in the management of prostate cancer, and methods of genomic tissue testing. He also emphasizes the difference between recreational genomics and genetic testing supervised and mentored by healthcare professionals.

Best Peter

To Read Peter's Comments - Click on the Link:

Link: Treatment Gene Testing
or Go To
http://rvaprostatecancersupport.org/PDF/1 18 20 Notes.pdf

To Watch “Genetics in Prostate Cancer: Identification of Inherited Prostate Cancer Risk” Video
Click on the Link:

Link: Genetics
or Go To
https://grandroundsinurology.com/genetics-in-prostate-cancer-identification-of-inherited-prostate-cancer-risk-2/

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Treatment Gene Testing

RVA - Us Too Warriors:

I made these comments at the meeting to help men determine at what stages in their treatment gene testing is valuable in planning your treatment . These are my comments

The Attached Video was shown at our Jan 16, 2020 meeting.
Genetics in Prostate Cancer: Identification of Inherited Prostate Cancer Risk –

Summary:
Leonard G. Gomella, MD, FACS, reviews basic concepts of genetics and genomics, the role of genetics and genomics testing in the management of prostate cancer, and methods of genomic tissue testing. He also emphasizes the difference between recreational genomics and genetic testing supervised and mentored by healthcare professionals.

Best Peter

To Read Peter's Comments - Click on the Link:

Link: Treatment Gene Testing
or Go To
http://rvaprostatecancersupport.org/PDF/1 18 20 Notes.pdf

To Watch “Genetics in Prostate Cancer: Identification of Inherited Prostate Cancer Risk” Video
Click on the Link:

Link: Genetics
or Go To
https://grandroundsinurology.com/genetics-in-prostate-cancer-identification-of-inherited-prostate-cancer-risk-2/

*
Genetics for PCa

Us Too warriors,

Statin use is associated with lower risk of PTEN-null and lethal prostate cancer

Abstract:

Background: Statins are associated with lower risk of aggressive prostate cancer, but lethal prostate cancer is understudied and contributing mechanisms unclear. We prospectively examined statins and lethal prostate cancer risk in the Health Professionals Follow-up Study (HPFS), tested associations with molecular subtypes, and integrated gene expression profiling to identify putative mechanisms. Methods: Our study included 44,126 men cancer-free in 1990, followed for prostate cancer incidence through 2014, with statin use recorded on biennial questionnaires. We used multivariable Cox regression to examine associations between statins and prostate cancer risk overall, by measures of clinically-significant disease, and by ERG and PTEN status. In exploratory analysis, age-adjusted gene set enrichment analysis identified statin-associated pathways enriched in tumor and adjacent normal prostate tissue.

Results: During 24 years follow-up, 6,305 prostate cancers were diagnosed and 801 (13%) were lethal (metastatic at diagnosis or metastatic/fatal during follow-up). Relative to never/past use, current statin use was inversely associated with risk of lethal prostate cancer (HR 0.76; 95%CI 0.60-0.96) but not overall disease. We found a strong inverse association for risk of PTEN-null cancers (HR 0.40; 95%CI 0.19-0.87) but not PTENintact cancers (HR 1.18; 95%CI 0.95-1.48; p-heterogeneity=0.01). Associations did not differ by ERG. Inflammation and immune pathways were enriched in normal prostate of statin ever (n=10) versus never users (n=103).

To Read More - Click on Our Link

Link: Genetics
or Go To
http://rvaprostatecancersupport.org/PDF/1 12 20 Allott-2019-Statin-use-is-associated-with-lower.pdf

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Repurposing screen identifies Mebendazole as a clinical candidate
to synergize with docetaxel for prostate cancer treatment

Us Too warriors,

BACKGROUND: Docetaxel chemotherapy in prostate cancer has a modest impact on survival. To date, efforts to develop combination therapies have not translated into new treatments. We sought to develop a novel therapeutic strategy to tackle chemoresistant prostate cancer by enhancing the efficacy of docetaxel.
METHODS: We performed a drug-repurposing screen by using murine-derived prostate cancer cell lines driven by clinically relevant genotypes. Cells were treated with docetaxel alone, or in combination with drugs (n = 857) from repurposing libraries, with cytotoxicity quantified using High Content Imaging Analysis.
RESULTS: Mebendazole (an anthelmintic drug that inhibits microtubule assembly) was selected as the lead drug and shown to potently synergise docetaxel-mediated cell killing in vitro and in vivo. Dual targeting of the microtubule structure was associated with increased G2/M mitotic block and enhanced cell death. Strikingly, following combined docetaxel and mebendazole treatment, no cells divided correctly, forming multipolar spindles that resulted in aneuploid daughter cells. Liposomes entrapping docetaxel and mebendazole suppressed in vivo prostate tumour growth and extended progression-free survival.
CONCLUSIONS: Docetaxel and mebendazole target distinct aspects of the microtubule dynamics, leading to increased apoptosis and reduced tumour growth. Our data support a new concept of combined mebendazole/docetaxel treatment that warrants further clinical evaluation.

To Read More - Click on Our Link

Link: Mebendazole
or Go To
http://rvaprostatecancersupport.org/PDF/1 9 20 PCa-mebendazole.pdf

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Advanced Prostate Cancer Clinic: What’s Changing? - Maha Hussain

Us Too warriors,

This video evaluates many of the ongoing clinical trials and the complexity of choice for PCa patients.

Maha Hussain highlights the pearls in the treatment landscape of metastatic hormone-sensitive, castration-resistant, and non-metastatic castration-resistant disease that came out of the last few years in prostate cancer in terms of the evolution of therapeutics. She details a plethora of clinical trials that had led to significant clinical benefit for patients, primarily overall survival advantages and improvement in the quality of life and pain control and provides her summary of where treatment stands and is headed in these disease spaces.

To see the Video - Click on Our Link

Link: Advanced Prostate Cancer Clinic
or Go To
https://www.urotoday.com/video-lectures/lugpa-2019/video/1615-advanced-prostate-cancer-clinic-what-s-changing-maha-hussain.html

*
Us Too warriors,

Docetaxel chemo is used up front In England before ADT. While in the USA , Docetaxel is often used later. Video discusses the reasons for the differences in approached.

To see the Video or read the Article - Click on Our Links

Link: Docetaxel
or Go To
https://www.urotoday.com/video-lectures/nmcrpc/video/mediaitem/1520-players-brightcove-net2019-10-09-17-03-56.html?utm_source=newsletter_7327&utm_medium=email&utm_campaign=2019-noteworthy-advances-in-treating-metastatic-hormone-sensitive-prostate-cancer

Link: Article
or Go To
https://www.urotoday.com/conference-highlights/esmo-2019/esmo-2019-prostate-cancer/115281-esmo-2019-docetaxel-for-hormone-naive-prostate-cancer-results-from-long-term-follow-up-of-non-metastatic-m0-patients-in-the-stampede-randomized-trial.html

*
Us Too warriors,

Genetic testing to detect cancer mutations is making progress in ADvanced Prostate cancer with the hope of finding a drug aim at the mutation or developing drugs to attack the many mutations in what is called precision medicine. I am planning to get a speaker to discuss these points for the January meeting.

This website video speaks to this point.
Molecular Genetic Testing in Prostate Cancer - Wassim Abida

Wassim Abida provides a current roadmap for molecular genetic subtyping in prostate cancer with the main goal of targeting the right therapies for progressing patients. The one clear indication for molecular testing at this point is in the identification of MSI-high prostate cancer because pembrolizumab is approved for this indication. Investigational PARP inhibitors (poly (ADP-ribose) polymerase inhibitor) is a substance that blocks an enzyme in cells called PARP. PARP helps repair DNA when it becomes damaged.

To see the Video - Click on Our Link

Link: Wassim Abida
or Go To
https://www.urotoday.com/video-lectures/molecular-diagnostics/video/mediaitem/1352-players-brightcove-net2019-06-20-23-14-14.html?utm_source=newsletter_7307&utm_medium=email&utm_campaign=prostate-cancer-daily

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Us TOO Presents: Prostate Cancer Pathways

Prostate Cancer Pathways Event and Webcast
Presented by Us TOO
Recorded Saturday, November 9, 2019
at Northwestern Medicine, Robert H. Lurie Medical Research Center
Chicago, IL

With Presenting Experts:

Sean Sachdev, MD - Radiation Treatment Options & Potential/ Probable Side Effects
Maha Hussain, MD - Advanced Prostate Cancer & Clinical Trials
Nelson Bennett, Jr., MD - Moderator & Sexual Health After Prostate Cancer Treatment
Carmen Williams, MS, CGC - Genetics & Genomics
Shilajit D. Kundu, MD - Initial Diagnosis: Active Surveillance, Surgical Options, Potential/Probable Side Effects from Surgery
Alicia Morgans, MD, MPH - Moderator
David J. VanderWeele, MD, PhD - Molecular Testing & Bone Support

To Read more and see the Video - Click on the Link BELOW:

(CLICK THE TIME FOR A DIRECT LINK TO EACH SEGMENT TOPIC AFTER YOU CLICK ON THE BELOW LINK)

Link: Pathways
or Go To
https://ustoo.org/PathwaysChicago2019

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Role of MDM2, PTEN, and TMPRSS2-ERG Fusions

RVA - Us Too Warriors:

Key Genes in Prostate Cancer Progression: Role of MDM2, PTEN, and TMPRSS2-ERG Fusions

Abstract
In recent years, multiple genes or their protein products have been linked to initiation and progression of prostate cancer. Such genes include TMPRSS2, ERG, PTEN, and MDM2. This chapter discusses the pathological roles as well as the potential diagnostic and therapeutic applications of these genes that are highly expressed in prostate cancer when compared to other cancer types. The presence of these genes and related defects are linked to growth, progression, metastasis, invasiveness and resistance in prostate cancers. While knowledge related to TMPRSS2, ERG, and PTEN have been accumulating in the last two decades, the prometastatic role of MDM2 has been emerging in the last few years and revealing important functions related to prostate cancer progression.The website video below is intriguing in showing live and dead cells produced in the sequence of treatments for advanced bone Pcancers and showing cells not responding which may be biopsied to determine mutations which may be treated by a different effective therapy!!

Best Peter

To Read more - Click on the Link:

Link: Progression
or Go To
http://rvaprostatecancersupport.org/PDF/12 25 19 Pten.pdf

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Imaging Bone (Flare) Responses

RVA - Us Too Warriors:

Imaging Bone (Flare) Responses in Advanced Prostate Cancer Presentation - Anwar Padhani

The website video below is intriguing in showing live and dead cells produced in the sequence of treatments for advanced bone Pcancers and showing cells not responding which may be biopsied to determine mutations which may be treated by a different effective therapy!!

Best Peter

To Read more and see the Video - Click on the Link:

Link: (Flare)
or Go To
https://www.urotoday.com/center-of-excellence/imaging-center/video-lectures/video/mediaitem/1450-players-brightcove-net2019-09-06-14-43-16.html?utm_source=newsletter_7296

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Melatonin

RVA - Us Too Warriors:

Melatonin May Increase Anticancer Potential of Pleiotropic Drugs

Abstract:
Melatonin (N-acetyl-5-methoxytryptamine) is not only a pineal hormone, but also an ubiquitary molecule present in plants and part of our diet. Numerous preclinical and some clinical reports pointed to its multiple beneficial effects including oncostatic properties, and as such, it has become one of the most aspiring goals in cancer prevention/therapy. A link between cancer and inflammation and/or metabolic disorders has been well established and the therapy of these conditions with so-called pleiotropic drugs, which include non-steroidal anti-inflammatory drugs, statins and peroral antidiabetics, modulates a cancer risk too. Adjuvant therapy with melatonin may improve the oncostatic potential of these drugs. Results from preclinical studies are limited though support this hypothesis, which, however, remains to be verified by further research

Best Peter

Also:
RVA Us Too Warriors, Most of my many antioxidant supplement polyphenols are designed to inhibit IL-6 stimulation of NFkb, But melatonin which I take at very high dose of 40 mg per night is very good at doing this and keeps ARV-7 from making Anti-Androgen therapies like Xtandi, casodex etc from failing from CRPC.
and
Melatonin Inhibits Androgen Receptor Splice Variant-7 (AR-V7)-Induced Nuclear Factor-Kappa B (NF-κB) Activation and NF-κB Activator-Induced AR-V7 Expression in Prostate Cancer Cells: Potential Implications for the Use of Melatonin in Castration-Resistant Prostate Cancer (CRPC) Therapy.

To Read more on these subjects - Click on the Links:

Link: IL-6 Stimulation
or Go To
http://rvaprostatecancersupport.org/PDF/2 8 20 PCa-Melatonin differentiates PCa and slows growth.pdf

Link: Variant-7 (AR-V7)
or Go To
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5485954/#__ffn_sectitle

Link: Anticancer Potential
or Go To
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320927/

and
Melatonin, a Full Service Anti-Cancer Agent: Inhibition of Initiation, Progression and Metastasis

Abstract:
There is highly credible evidence that melatonin mitigates cancer at the initiation, progression and metastasis phases. In many cases, the molecular mechanisms underpinning these inhibitory actions have been proposed. What is rather perplexing, however, is the large number of processes by which melatonin reportedly restrains cancer development and growth. These diverse actions suggest that what is being observed are merely epiphenomena of an underlying more fundamental action of melatonin that remains to be disclosed. Some of the arresting actions of melatonin on cancer are clearly membrane receptor-mediated while others are membrane receptor-independent and involve direct intracellular actions of this ubiquitously-distributed molecule. While the emphasis of melatonin/cancer research has been on the role of the indoleamine in restraining breast cancer, this is changing quickly with many cancer types having been shown to be susceptible to inhibition by melatonin. There are several facets of this research which could have immediate applications at the clinical level. Many studies have shown that melatonin’s co-administration improves the sensitivity of cancers to inhibition by conventional drugs. Even more important are the findings that melatonin renders cancers previously totally resistant to treatment sensitive to these same therapies. Melatonin also inhibits molecular processes associated with metastasis by limiting the entrance of cancer cells into the vascular system and preventing them from establishing secondary growths at distant sites. This is of particular importance since cancer metastasis often significantly contributes to death of the patient. Another area that deserves additional consideration is related to the capacity of melatonin in reducing the toxic consequences of anti-cancer drugs while increasing their efficacy. Although this information has been available for more than a decade, it has not been adequately exploited at the clinical level. Even if the only beneficial actions of melatonin in cancer patients are its ability to attenuate acute and long-term drug toxicity, melatonin should be used to improve the physical wellbeing of the patients. The experimental findings, however, suggest that the advantages of using melatonin as a co-treatment with conventional cancer therapies would far exceed improvements in the wellbeing of the patients.

To Read more on this subject - Click on the Links:

Link: Full Service
or Go To
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5412427/

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Mushroom Consumption
RVA Us Too Warriors:

Mushroom consumption and incident risk of prostate cancer in Japan: A pooled analysis of the Miyagi Cohort Study and the Ohsaki Cohort Study

Introduction
According to Global Cancer Statistics 2018,1 prostate cancer ranks as the second-most frequent cancer and the ﬁfth leading cause of cancer death in men. Although there is no sure way to prevent prostate cancer, maintaining healthy eating habits (e.g., consuming more vegetables and fruits) has been suggested as an approach that might lower the risk of prostate cancer.

Mushrooms have a long history of being consumed as food and used in Asian medicines. However, research on the health effects of mushrooms has only emerged and been developed in recent decades. To date, an increasing number of in vivo and in vitro studies have suggested the beneﬁcial effects of mushrooms on health, such as antioxidation, anti-inﬂammation, immunomodulation, etc.

Additionally, mushrooms also reportedly have anticancer properties and effects against tumor development.In vivo and in vitro evidence has shown that mushrooms have the potential to prevent several kinds of cancers (e.g., those of the breast, bladder, colon and lung), including prostate cancer. Extracts of mushrooms such as Agaricus blazei Murill, Agaricus bisporus, Trametes versicolor, Cordyceps militaris and Coprinus comatus were suggested to inhibit cell proliferation in human prostate cancer cell lines and to restrict prostate tumorigenic progression from the hormone-dependent to the hormonerefractory state.

To Read more on this subject - Click on the Link:

Link: Mushroom
or Go To
http://rvaprostatecancersupport.org/PDF/12 15 19 Zhang_et_al-2019-International_Journal_of_Cancer.pdf

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Apalutamide Versus Enzalutamide

Matching-Adjusted Indirect Comparison of Health-Related Quality of Life and Adverse Events of Apalutamide Versus Enzalutamide in Non-Metastatic Castration-Resistant Prostate Cancer.

Abstract

INTRODUCTION:
The present study aimed to indirectly compare apalutamide and enzalutamide with respect to tolerability and health-related quality of life (HRQoL) among men with non-metastatic castration-resistant prostate cancer (nmCRPC).

METHODS:
Patient-level data from the SPARTAN study [apalutamide + androgen deprivation therapy (ADT) versus placebo + ADT] and aggregate published data from the PROSPER study (enzalutamide + ADT versus placebo + ADT) were used. Anchored matching-adjusted indirect comparison (MAIC) was conducted by weighting patients' baseline characteristics from SPARTAN to match aggregated baseline characteristics in PROSPER. Odds ratios (ORs) of reported adverse events (AEs) and baseline-to-follow-up least squares mean differences in HRQoL [measured with Functional Assessment of Cancer Therapy-Prostate (FACT-P) score] with 95% credible intervals were re-estimated for SPARTAN arms using weighted population and indirectly compared with those in PROSPER through a Bayesian framework. Events of special interest included fatigue, hot flush, nausea, diarrhea, hypertension, falls, dizziness, decreased appetite, arthralgia, asthenia and headache. In addition, any AEs and serious AEs were explored.

To Read more on this subject - Click on the Link:

Link: Apalutamide Versus Enzalutamide
or Go To
https://www.ncbi.nlm.nih.gov/pubmed/31813087

*
US Dept. Veterans Affairs

VA, Prostate Cancer Foundation seek solutions for aggressive prostate cancer.

While in treatment for an aggressive form of prostate cancer at the VA Puget Sound Health Care System in Seattle, Navy Veteran Allen Petchnick faced a daunting situation. His PSA blood test, the main screening tool for cancer of the prostate, had risen to 13, which for him was dangerously high. Plus, his cancer had spread to other parts of his body.

“He was looking at very tough outcomes,” says Dr. Bruce Montgomery, an oncologist at VA Puget Sound. “He was passing out because his tumor had metastasized to lymph nodes in his neck, which was pressing against one of his arteries.”

Montgomery led a medical team that performed next-generation sequencing, an innovative way to sequence the human genome at high speed and low cost, on tissue in Petchnick’s lymph nodes. They spotted mismatch repair (MMR) deficient cells, which usually have many genetic mutations—the changing of the structure of a gene—that may lead to cancer. Knowing if a tumor is MMR-deficient may help clinicians plan treatment or predict how the tumor will respond to treatment. This is an example of precision oncology.

To Read more on this subject - Click on the Link:

Link: Aggressive Prostate Cancer
or Go To
https://www.research.va.gov/currents/1119-VA-and-Prostate-Cancer-Foundation-seek-solutions-for-aggressive-prostate-cancer.cfm

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PARP INHIBITION THERAPY

RVA Us Too Warriors:

PARP INHIBITION THERAPY — Clinical importance of genetic variants of BRCA 1/2 and ATM in men with metastatic castration-resistant prostate cancer.

Something big is emerging in the management of men with metastatic (often heavily pre-treated) castration-resistant prostate cancer: A new potential entry into the regimens of standard-of-care treatment of men with BRCA 1/2 and ATM mutations with PARP inhibitor therapy.

This Commentary is offered as a heads-up to seed clinical awareness that this rapidly evolving category of management is an option. It should be considered for all men with metastatic cancer who harbor these gene variants and are progressing despite current therapies..

To Read more comments on this subject - Click on the Link:

Link: PARP INHIBITION THERAPY
or Go To
http://rvaprostatecancersupport.org/PDF/12 9 19 PARP INHIBITION THERAPY.pdf

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A Better Description of the BAT Therapy

RVA Us Too Warriors:

The male hormone testosterone can feed the growth of prostate cancer, but in an interesting twist, when given in a very specific way, it may also cause its demise. Drugs that block the action of testosterone are commonly used to treat men with advanced prostate cancer therapy. Cutting off the supply of testosterone to the cancer works for a time, but eventually prostate cancer cells figure out a way around it and begin to grow again. Other drugs work at the molecular level to cut off prostate cancer cells’ access to testosterone, but their impact is temporary and comes with unpleasant side effects. “Men who have long-term hormone ablation have a good response initially, but eventually they become resistant to therapy, and then there aren’t many options left for them,” says prostate cancer expert Samuel Denmeade. These are the men most at risk of dying from prostate cancer.

To Read more on this subject - Click on the Link:

Link: BAT
or Go To
https://www.hopkinsmedicine.org/news/articles/testosterone-as-a-drug

*
Bipolar Androgen Therapy for Men with Castration Resistant Prostate Cancer

RVA Us Too Warriors:

Washington, DC (UroToday.com) As part of the SUO 2019 advanced prostate cancer session, Dr. Samuel Denmeade discussed his work with bipolar androgen therapy (BAT) for men with castration resistant prostate cancer (CRPC). Dr. Denmeade reminds us that metastatic prostate cancer remains an incurable disease, with a median overall survival in the CRPC state of three years. The mainstay of treatment is androgen deprivation therapy (ADT), however it is associated with many side effects:
Best
Peter

To Read more on this subject - Click on the Link:

Link: Bipolar Androgen Therapy
or Go To
https://www.urotoday.com/conference-highlights/suo-2019/suo-2019-prostate-cancer/117595-suo-2019-bipolar-androgen-therapy-for-men-with-castration-resistant-prostate-cancer.html

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Peripheral Neuropathy

RVA Us Too Warriors:

Preventing peripheral neuropathy during Taxotere treatment.

A question: I will be starting Taxotere soon. Has anyone used the cold gloves and footwear to avoid issues with peripheral neuropathy, and how successful were they in avoiding this side effect? Thanks in advance for your response.

Best
Peter

To Read more comments on this subject - Click on the Link:

Link: Peripheral Neuropathy
or Go To
http://rvaprostatecancersupport.org/PDF/12 8 19 Preventing peripheral neuropathy during Taxotere treatment.pdf

*
Chemohormonal Sequencing

RVA Us Too Warriors:

Optimal chemohormonal sequencing for mCRPC MAY be Taxotere->Zytiga->Jevtana->Xtandi

(1) Taxotere (docetaxel) first

In a retrospective study presented at the Society for Urologic Oncology meeting, researchers at the Mayo Clinic reported on 112 patients with metastatic castration-resistant prostate cancer (mCRPC).

Group A (80 men) had docetaxel (Taxotere) followed by one of the second-line hormonal therapies: either abiraterone (Zytiga) or enzalutamide (Xtandi)
Group B (32 men) had a second-line hormonal therapy followed by Taxotere.
Bone metastases were more common in Group B (87%) than Group A (58%)

This was not a prospective randomized clinical trial. It reaches a different conclusion from a couple of earlier retrospective analyses. Sonpavde et al. reported an analysis of 1445 patients at VA hospitals.

Best
Peter

To Read more on this subject - Click on the Link:

Link: Chemohormonal Sequencing
or Go To
http://rvaprostatecancersupport.org/PDF/12 8 19 mCRPC.pdf

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Bone Metastases

RVA Us Too Warriors:

Colorado study suggests new strategies against bone metastases from prostate cancer

When prostate cancer spreads, it most often spreads to bone. And while the 5-year survival rate for prostate cancer that has not spread is nearly 100 percent, once the disease reaches bone, the 5-year survival rate is only 29 percent. Now a University of Colorado Cancer Center study published in the Journal for Immunotherapy of Cancer suggests a new approach, or, possibly two new approaches against these bone metastases: While targeted therapies and anti-cancer immunotherapies have not been especially successful against primary prostate cancers, the study suggests that both these approaches may be effective against the bone metastases that grow from primary prostate cancers, and, in fact, the type of bone metastasis may dictate which targeted therapies and immunotherapies work best.

Best
Peter

To Read more on this subject - Click on the Link:

Link: Bone Metastases
or Go To
https://eurekalert.org/pub_releases/2019-12/uoca-css120219.php

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Ursolic acid

RVA Us Too Warriors:

Ursolic acid and its derivative inhibit protein tyrosine phosphatase 1B, enhancing insulin receptor phosphorylation and stimulating glucose uptake.
It is found in the Herb Sage.

Protein tyrosine phosphatase 1B (PTP1B) is a key element in the negative regulation of the insulin signaling pathway and may play an important role in diabetes and obesity. We identified ursolic acid, a natural pentacyclic triterpenoid that occurs widely in traditional Chinese medicinal herbs, as an inhibitor of PTP1B by screening an extract library of the traditional Chinese medicinal herbs used a diabetes clinic. By modifying urosolic acid, we designed and synthesized a derivative with a Ki of 283 nM. As competitive inhibitors of PTP1B, ursolic acid and its derivative also inhibit T-cell protein tyrosine phosphatase and src homology phosphatase-2 but not leucocyte antigen-related phosphatase or protein tyrosine phosphatase α and ε, which are all possibly involved in the insulin pathway. The ursolic acid derivative enhanced insulin receptor phosphorylation in CHO/hIR cells and stimulate glucose uptake in L6 myotubes.
Best
Peter

To Read more on this subject - Click on the Link:

Link: Ursolic acid
or Go To
http://rvaprostatecancersupport.org/PDF/12 2 19 1-s2.0-S0167488912003680-main.pdf

To Read more on the Website - Click on the Link:

Link: Website
or Go To
https://www.sciencedirect.com/science/article/abs/pii/S0304416506001607

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Pterostilbene
RVA Us Too Warriors:

Dietary pterostilbene is a novel MTA1-targeted chemopreventive and therapeutic agent in prostate cancer (FoTi = Knot Weed = he shou wu).

Overexpression of the epigenetic modifier metastasis-associated protein 1 (MTA1) is associated with aggressive human prostate cancer. The purpose of this study was to determine MTA1- targeted chemopreventive and therapeutic efficacy of pterostilbene, a natural potent analog of resveratrol, in pre-clinical models of prostate cancer. Here, we show that high levels of MTA1 expression in Pten-loss prostate cooperate with key oncogenes, including c-Myc and Akt among others, to promote prostate cancer progression. Loss-of-function studies using human prostate cancer cells indicated direct involvement of MTA1 in inducing inflammation and epithelialto-mesenchymal transition. Importantly, pharmacological inhibition of MTA1 by pterostilbene resulted in decreased proliferation and angiogenesis and increased apoptosis. This restrained prostatic intraepithelial neoplasia (PIN) formation in prostate-specific Pten heterozygous mice and reduced tumor development and progression in prostate-specific Pten-null mice. Our findings highlight MTA1 as a key upstream regulator of prostate tumorigenesis and cancer progression. More significantly, it offers pre-clinical proof for pterostilbene as a promising lead natural agent for MTA1-targeted chemopreventive and therapeutic strategy to curb prostate cancer.
Best
Peter

To Read more on this subject - Click on the Link:

Link: Pterostilbene
or Go To
http://rvaprostatecancersupport.org/PDF/11 30 19 7841-119271-4-PB.pdf

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Dementia and Depression
RVA Us Too Warriors:

Risk of Dementia and Depression in Young and Middle-aged Men Presenting with Nonmetastatic Prostate Cancer Treated with Androgen Deprivation Therapy.

BACKGROUND: Previous studies have found an association between androgen deprivation therapy (ADT) and an increased risk of dementia and depression in elderly men. This association remains controversial, and little is known about the effects of ADT in younger men.

OBJECTIVE: To examine the association between the receipt of ADT and these outcomes in young men aged 40-64 yr presenting with nonmetastatic prostate cancer (PCa).

Best Peter

To Read more on this subject - Click on the Link:

Link: Dementia and Depression
or Go To
https://www.ncbi.nlm.nih.gov/pubmed/31624049

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Cabazitaxel
RVA Us Too Warriors:

Overall and progression-free survival with cabazitaxel in metastatic castration-resistant prostate cancer in routine clinical practice: the FUJI cohort.

BACKGROUND: Cabazitaxel is a treatment of metastatic castration-resistant prostate cancer (mCRPC) after docetaxel failure. The FUJI cohort aimed to conﬁrm the real-life overall and progression-free survival (OS, PFS) and safety of cabazitaxel.
METHODS: Multicentre, non-interventional cohort of French mCRPC patients initiating cabazitaxel between 2013 and 2015, followed 18 months.
RESULTS: Four hundred one patients were recruited in 42 centres. At inclusion, median age was 70, main metastatic sites were bones (87%), lymph nodes (42%) and visceral (20%). 18% had cabazitaxel in 2nd-line treatment, 39% in 3rd-line and 43% in 4th-line or beyond. All had prior docetaxel, and 82% prior abiraterone, enzalutamide or both. Median duration of cabazitaxel treatment was 3.4 months. Median OS from cabazitaxel initiation was 11.9 months [95% CI: 10.1–12.9]. In multivariate analyses, grade≥3 adverse events, visceral metastases, polymedication, and >5 bone metastases were associated with a shorter OS. Main grade≥3 adverse events were haematological with 8% febrile neutropenia.
CONCLUSION: Real-life survival with cabazitaxel in FUJI was shorter than in TROPIC (pivotal trial, median OS 15.1 months) or PROSELICA (clinical trial 20 vs 25mg/m2, median OS, respectively, 13.4 and 14.5 months). There was no effect of treatment-line on survival. No unexpected adverse concerns were identiﬁed. STUDY REGISTRATION: It was registered with the European Medicines Agency EUPASS registry, available at www.encepp.eu, as EUPAS10391. It has been approved as an ENCEPP SEAL study.
Best
Peter

To Read more on this subject - Click on the Link:

Link: Cabazitaxel
or Go To
http://rvaprostatecancersupport.org/PDF/11 29 19 Rouyer-2019-Overall-and-progression-free-surviv.pdf

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Theranostic Approaches for Advanced Prostate Cancer - Michael Hofman
RVA Us Too Warriors:

Professor Michael Hofman presented on prostate-specific membrane antigen (PSMA) targeted therapies during the Management of castration-resistant prostate cancer (CRPC) session at the Advanced Prostate Cancer Consensus Conference (APCCC) 2019, presenting data from both of his groups in Australia. Dr. Hofman highlights the progress of a single-centre, single-arm, phase 2 study; [177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer of which in 2015, his group started enrolling. Before concluding, Dr. Hofman highlights several trials with 177Lu-PSMA that are ongoing.
Best Peter

To Read more on this subject and see the Video - Click on the Link:

Link: Theranostic
or Go To
https://www.urotoday.com/center-of-excellence/imaging-center/video-lectures/video/mediaitem/1155-embedded-media2019-02-23-19-51-36.html

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Statin Use
RVA Us Too Warriors:

Statin Use is associated with lower risk of PTEN-null and lethal prostate cancer.
Best Peter

To Read more on this subject - Click on the Link:

Link: Statin Use
or Go To
http://rvaprostatecancersupport.org/PDF/11 25 19 10.1158_1078-0432.CCR-19-2853.pdf

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Enzalutamide
RVA Us Too Warriors:

My Brother has responded well to enzalutamide for over four years and I have used Casodex going on 2 years (Cancer considered undetectable because PSA<0.1),
both are blockers of the Androgen receptor. We both have germline mutation of TMPRSS2-ERG. The attached paper predicts we should have a good response with
this mutation from AR Blockers (50% of men have this mutation) that we have experienced.
All Best,
Peter

To Read more on this subject - Click on the Link:

Link: Enzalutamide
or Go To
http://rvaprostatecancersupport.org/PDF/11 16 19 PCa-TMPRSS2-ERG fusions confer efficacy of enzalutamide because of its higher hormone sensitive cancer.pdf

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Lutetium-177

Objectives: Lutetium-177 (177Lu)-PSMA-617 (LuPSMA) is a radioligand with high affinity for prostate specific membrane antigen (PSMA) enabling targeted beta-irradiation of prostate cancer. We have previously reported favorable activity with low toxicity in a prospective phase II trial involving 30 men with metastatic castrate-resistant prostate cancer (mCRPC). We now report their longer-term outcomes including a 20 patient extension cohort and outcomes of subsequent systemic treatments following completion of trial therapy.

To Read more on this subject - Click on the Link:

Link: Lutetium-177
or Go To
http://rvaprostatecancersupport.org/PDF/11 16 19 10.2967_jnumed.119.236414.pdf

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ASCO GU 2019: Biologic Basis for Sequencing Novel Treatments for Metastatic Prostate Cancer

San Francisco, CA (UroToday.com) Dr. Beltran presented a summary of the biologic basis for sequencing novel treatments for metastatic prostate cancer.

There is an increasing need for biomarkers in advanced prostate cancer management – as there is a plethora of treatment options without much guidance about selection or sequencing. Some of the areas that require work are:

•Choice of Androgen receptor (AR) pathway inhibitor vs. docetaxel for castration-sensitive prostate cancer (CSPC)
•Optimal sequencing of approved drugs for castration-resistant prostate cancer (CRPC)
•Patient selection for targeted therapy or immunotherapy
•Early detection of treatment resistance
•Design of rational combination therapies

She then touched upon the fact that metastatic biopsies are increasingly being utilized (either biopsy of the met directly or liquid biopsies) to look for actionable targets OR to identify treatment resistance.

Click on the Link to Read more:

Link: Novel Treatments
or Go To
https://www.urotoday.com/conference-highlights/asco-gu-2019/asco-gu-2019-prostate-cancer/110280-asco-gu-2019-biologic-basis-for-sequencing-novel-treatments-for-metastatic-prostate-cancer.html
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Benefit of Taxanes

The Abstract results of a Clinic Trial at J. Hopkins show the benefit of Taxanes on treatment of advanced PCa in patients with the short androgen receptor AR-A7 especially for men that fail Xtandi or Zytiga.
All the Best
Peter

Click on the Link to Read more:

Link: Taxanes
or Go To
https://www.ncbi.nlm.nih.gov/pubmed/26181238#
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Everyday Urology - Volume 4, Issue 3

From the Desk of the Editor: Volume 4, Issue 3

Welcome to Everyday Urology - Oncology Insights. As is our journal’s goal, this issue will illuminate recent advances within the management armamentarium of Urologic Oncology by featuring clinical care updates and expert opinions. In this issue, Everyday Urology focuses on advanced prostate cancer, highlighting recent additions to the nmCRPC treatment landscape as well as the emerging role of theranostics. Finally, our spotlight features coverage of the Advanced Prostate Cancer Consensus Conference, (APCCC 2019) held August 29 - 31, 2019 in Basel, Switzerland.

Click on the Link to Read more:

Link: Issue 3
or Go To
https://www.urotoday.com/journal/everyday-urology-oncology-insights.html
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Centers of Excellence - Advanced Prostate Cancer

The below link will take you to State-of-the-industry video lectures by leading urology experts covering various areas of Prostate Cancer.

Two Examples of the various Topics:

Assessment of Cardiovascular Risk With the Use of Androgen Deprivation Therapy for Prostate Cancer By Matthew T. Roe, MD, MHS, MHS

Heart disease and cancer are the leading causes of death in the United States.1 Prostate cancer (PC) is the most common cancer in American men, and PC is most frequently diagnosed among men aged 65 to 74 years.2 The American Cancer Society’s estimates for PC in the United States for 2017 are about 161,360 new cases. Of these, about 26,730 are expected to die of the disease.

Update on ADT in Advanced Prostate Cancer By Thomas E. Keane, MBBCh, FRCSI, FACS

Prostate cancer is the leading incident cancer among men, and population growth and aging have fueled a 40% rise in global case burden since 2006.1,2 Despite recent improvements in treatment, patients with locally advanced and advanced prostate cancer experience significant emotional distress, diminished quality of life, and increased risk of cancer-specific mortality

Click on the Link to Read more:

Link: Video Lectures
or Go To
https://www.urotoday.com/center-of-excellence/advanced-prostate-cancer.html
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Malecare’s Advanced Prostate Cancer newsletter

Signing up for Malecare’s Advanced Prostate Cancer newsletter is easy. Just enter your email address after clicking on the link below. You can unsubscribe at any time.

You might be interested in this Blog.
Example of one subject - PSA time to nadir as a prognostic factor of first-line docetaxel treatment in CRPC
Also they have - See others who are similar to you 'Similar to me' is a new feature that helps you find other members with similar profiles to yours.

Click on the Link to Sign up:

Link: Sign Up
or Go To
https://malecare.org/advanced-prostate-cancer-newsletter

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Castration-resistant Prostate Cancer.

Clinical Utility of the Nuclear-localized AR-V7 Biomarker in Circulating Tumor Cells in Improving Physician Treatment Choice in Castration-resistant Prostate Cancer.

Proof of the clinical utility of a biomarker is when its use informs a management decision and improves patient outcomes relative to when it is not used.

To model the clinical benefit of the nuclear-localized androgen receptor splice variant 7 (AR-V7) test for men with progressing metastatic castration-resistant prostate cancer (mCRPC) at the second line of therapy or greater to inform the choice of an androgen receptor signaling inhibitor (ARSI) or a taxane.
To Read more on this subject Click on the Link:

Link: AR-V7
or Go To
https://www.urotoday.com/recent-abstracts/urologic-oncology/prostate-cancer/116090-clinical-utility-of-the-nuclear-localized-ar-v7-biomarker-in-circulating-tumor-cells-in-improving-physician-treatment-choice-in-castration-resistant-prostate-cancer.htm

A Third-line Therapy Option

Results of the CARD trial: Benefit for patients needing a third-line therapy option

Metastatic castration-resistant prostate cancer (mCRPC) refers to prostate cancer that has spread outside the prostate and no longer responds to traditional androgen deprivation therapy (ADT). Patients have several different treatment options, including second-generation androgen-signaling-targeted inhibitors (ARTA) like abiraterone or enzalutamide, and chemotherapy drugs (docetaxel, cabazitaxel). However, for patients whose disease progresses after treatment with one ARTA and with docetaxel, questions remain: Should the patient switch to the other ARTA? Should a chemotherapy drug be used?

To Read more on this subject Click on the Link:

Link: Option
or Go To
https://www.pcf.org/news/results-of-the-card-trial-benefit-for-patients-needing-a-third-line-therapy-option/

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Genetics of Prostate Cancer

RVA Us Too Warriors:

All in the Family: Genetics of Prostate Cancer

Cancer is a Genetic Disease

• ALL cancer is genetic. • Mutations in genes lead to cancer development. • These mutations can be acquired or inherited. • Testing for these gene mutations can guide therapy and/or cancer screening.

To Read more on this subject and see the slides Click on the Link:

Link: Family
or Go To
http://rvaprostatecancersupport.org/PDF/10 30 19 GeneticsHandoutColor_SendByEmail.pdf

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TMPRSS2-ERG Gene

RVA Us Too Warriors:

Hyperglycemia Promotes TMPRSS2-ERG Gene Fusion in Prostate Cancer Cells via Upregulating Insulin-Like Growth Factor-Binding Protein-2

Background: Epidemiologic evidence shows that obesity is associated with a greater risk of aggressive prostate cancer (PCa) and PCa-specific mortality and this is observed mainly in men with the TMPRSS2-ERG gene fusion. Obesity is often associated with comorbid conditions such as type 2 diabetes and hyperglycemia: we investigated whether some of the exposures associated with disturbed metabolism can also affect the frequency of this gene fusion.

Methods: Fusion was induced in LNCaP PCa cells in normal or high levels of glucose, with or without insulin-like growth factor binding protein-2 (IGFBP-2) silenced or the presence of insulin-like growth factor-1 (IGF-I), insulin, or epidermal growth factor (EGF). RNA was extracted for analysis by nested PCR. Abundance of IGFBP-2, γH2AX, DNAdependent protein kinase catalytic subunit (DNAPKcs), and β-actin were analyzed by Western immunoblotting.

To Read more on this subject:

Link: TMPRSS2
or Go To
http://rvaprostatecancersupport.org/PDF/10 29 19 PCa-Hyperglycemia Promotes TMPRSS2-ERG Fusion by upregulation IGF-BP2 fendo-08-00305.pdf

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AR-V7
RVA Us Too Warriors:

Androgen Receptor Splice Variant, AR-V7, as a Biomarker of Resistance to Androgen Axis-Targeted Therapies in Advanced Prostate Cancer.

Many therapeutic options are now available for men with metastatic castration-resistant prostate cancer (mCRPC), including next-generation androgen receptor axis-targeted therapies (AATTs), immunotherapy, chemotherapy, and radioisotope therapies. No clear consensus has been reached for the optimal sequencing of treatments for patients with mCRPC, and few well-validated molecular markers exist to guide the treatment decisions for individual patients. The androgen receptor splice variant 7 (AR-V7), a splice variant of the androgen receptor mRNA resulting in the truncation of the ligand-binding domain, has emerged as a biomarker for resistance to AATT. AR-V7 expression in circulating tumor cells has been associated with poor outcomes in patients treated with second- and third-line AATTs.

Click on Our Link to read more - AR-V7
or Go To
https://www.urotoday.com/recent-abstracts/urologic-oncology/prostate-cancer/116067-androgen-receptor-splice-variant-ar-v7-as-a-biomarker-of-resistance-to-androgen-axis-targeted-therapies-in-advanced-prostate-cancer.html
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HIF-1 Genes/Proteins pathway
RVA Us Too Warriors:

High levels of HIF-1 genes/proteins pathway makes PCa recur. Read and see attachments following about how to fight it. The natural inhibitors of Heat Shock Protein 90 that I talked about at our June 2019 meeting are easiest way to apply this knowledge now, until some expensive drug is FDA proves sometime in the future. Many flavonoids were found to be inhibitors of phosphatidylinositol 3-kinase/AKT signaling. Chrysin inhibited AKT activation. Thus, it is conceivable that chrysin may also inhibit HIF-1a via AKT signaling. It was reported that flavonoids or related compounds, such as apigenin (28, 46), resveratrol (47), and ()-epigallocatechin-3-gallate (48), inhibited expression of HIF-1a through multiple pathways, including protein synthesis and protein degradation.

Other natural inhibitors are berberine, and quercetin and Chrysin!!! Many of these Block the heat Shock Protein 90 from promoting HIF-1 which I talked about in June 2019 as a way to fight your cancer by blocking PIK3/AKT/ mTOR cancer pathways which is prominent growth by many PCa gene mutations like BRACA and Pten mutations.

PARP inhibitor drugs are now available to block PIK3/AKT/ mTOR cancer pathways are used BRACA and Pten mutated PCa among others but they work for relative short times ~1 < 2 years. Fruit enriched diet will contain many of the natural inhibitors which can be fortified with supplements from Swanson etc.

To Read more on this subject:

Link 1 - Hypoxia inducible factor pathway inhibitors
Link 2 - Natural Product-Based Inhibitors
Link: Hypoxia inducible factor pathway inhibitors
or Go To
http://rvaprostatecancersupport.org/PDF/10 18 19 PCa-HIF-1 Hypoxia inducible factor pathway inhibitors as anticancer therapeutics.pdf

Link: Natural Product-Based Inhibitors
or Go To
http://rvaprostatecancersupport.org/PDF/10 18 19 PCa-Natural Product-Based Inhibitors of Hypoxia-Inducible Factor-1 to prevent PCa recurrence.pdf

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Advanced Cancer with Castration Resistance
RVA Us Too Warriors:

In advanced cancer with castration resistance, Xtandi and Zytiga fail even on ADT because the Androgen receptor is Shortened (AR-V7) so that it is always active causing the cancer to grow even when testosterone is extremely low. The Clinical trial below tests Niclosamide At UCLA to overcome this problem. And at the end of the trial are attached two papers attached describing the blood tests for your information- One is test is from John Hopkins.

To Read more on this subject:

Link: Resistance
or Go To
http://rvaprostatecancersupport.org/PDF/10 16 19 PCa-AR-V7 and its Clinical Correlates in Metastatic Castration-resistant PCa.pdf

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Background on Genetics

Some Background on Genetics that may help in your cancer Fight with the Guardian 360 blood test.

The first link is a paper on - Genetics and biology of prostate cancer

The second link is on - Evaluation of Commercial Circulating Tumor DNA Test in Metastatic Prostate Cancer

Click on Our Link to read more - Genetics
or Go To
http://rvaprostatecancersupport.org/PDF/10 16 19 PCa-Genetics and biology of prostate cancerGenes Dev.-2018-Wang-1105-40.pdf

Click on Our Link to read more - Evaluation
or Go To
http://rvaprostatecancersupport.org/PDF/10 16 19 Taavitsainen-2019-Evaluation-of-commercial-circulatin.pdf
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PSMA-targeted Therapies

The first link is a paper on - PCa-Prostate-specific Membrane Antigen Heterogeneity and DNA repair mutations

The second link is on PSMA-targeted Therapies which Work Best in Tumors with Mutations in DNA Repair Genes, The Study Suggests

Click on Our Link to read more - Heterogeneity
or Go To
http://rvaprostatecancersupport.org/PDF/10 16 19 PCa-Prostate-specific Membrane Antigen Heterogeneity and DNA repair mutations.pdf

Click on Our Link to read more - PSMA
or Go To
https://prostatecancernewstoday.com/2019/08/22/psma-therapies-most-effective-in-tumors-with-dna-repair-gene-mutations-study-finds/
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Treatment of Metastatic Castration-Resistant Prostate Cancer

Janssen Announces U.S. FDA Breakthrough Therapy Designation Granted for Niraparib for the Treatment of Metastatic Castration-Resistant Prostate Cancer, is currently being investigated for the treatment of patients with metastatic castration-resistant prostate cancer and BRCA1/2 DNA repair gene defects.

RARITAN, N.J., October 3, 2019 – The Janssen Pharmaceutical Companies of Johnson & Johnson announced today that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation for niraparib, an orally-administered poly ADP-ribose polymerase (PARP) inhibitor, for the treatment of patients with BRCA1/2 gene-mutated metastatic castration-resistant prostate cancer (mCRPC) who have received prior taxane chemotherapy and androgen receptor (AR)-targeted therapy. A Breakthrough Therapy Designation is granted to expedite the development and regulatory review of an investigational medicine that is intended to treat a serious or life-threatening condition.1 The criteria for Breakthrough Therapy Designation require preliminary clinical evidence that demonstrates the drug may have substantial improvement on at least one clinically significant endpoint over available therapy.[1]

Click on Our Link to read more - Niraparib
or Go To
https://www.prnewswire.com/news-releases/janssen-announces-us-fda-breakthrough-therapy-designation-granted-for-niraparib-for-the-treatment-of-metastatic-castration-resistant-prostate-cancer-300930955.html
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AR Targeing in Non-CRPC ---- Can we do beter?

These slides show the many advanced treatments for advanced cancer without talk so you have to study the graphs to decipher what is going on.

Click on Our Link to read more - Non-CRP
or Go To
http://rvaprostatecancersupport.org/PDF/PCa-Ryan Slides-AR Target-Early.pdf
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Circulating tumor cells(CTC) - which will show the # of these cells in 7.5 ml of blood. If the cells are less than 5 the survival is favorable. So I will check cell numbers now to know for a baseline and after 3 months of treatment to see if the treatment is working by lowering the number of circulating cancer cells. A new treatment is yet to be decided but I expect it to be Casodex. If I see signs of PSA increasing after I have been on treat for a while assuming the treatment works to bring down the PSA as expected, I will get additional CTC test to see what is going on.

Information about the CTC tests can be found at this website:

Click on Our Link to read more
CTC
or Go To
https://www.cellsearchctc.com/about-cellsearch/what-is-cellsearch-ctc-test

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Prostate cancer's penchant for copper may be a fatal flaw (6/21/18)

Prostate cancer's penchant for copper may be a fatal flaw
Published Friday 17 October 2014
Adapted Media Release

Like discriminating thieves, prostate cancer tumors scavenge and hoard copper that is an essential element in the body. But such avarice may be a fatal weakness.

Click on Our Link to Read this latest information

Link: Copper
or Go To
https://www.sciencedaily.com/releases/2014/10/141015084514.htm
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CDK4/6 Therapeutic Intervention and Viable Alternative to Taxanes in CRPC
Resistance to second-generation androgen receptor (AR) antagonists and CYP17 inhibitors in patients with castrationresistant prostate cancer (CRPC) develops rapidly through reactivation of the androgen signaling axis and has been attributed to AR overexpression, production of constitutively active AR splice variants, or the selection for AR mutants with altered ligandbinding specificity. It has been established that androgens induce cell-cycle progression, in part, through upregulation of cyclin D1 (CCND1) expression and subsequent activation of cyclin-dependent kinases 4 and 6 (CDK4/6).
Click on Our Link to read more - CDK4
or Go To
http://rvaprostatecancersupport.org/PDF/PCa-CDK4-6 looks better than taxanes if enzalutamide fails Mol Cancer Res-2017-Stice.pdf
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Metformin reverses prostate cancer resistance to enzalutamide by targeting TGF-β1/STAT3 axis-regulated EMT.
Click on Our Link to read more - Metformin
or Go To
https://www.ncbi.nlm.nih.gov/pubmed/28837141
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A Randomized-Controlled Trial of Transcutaneous Oestrogen Patches Versus LHRH Agonists in Prostate Cancer
Click on Our Link to read more - Patches
or Go To
https://www.urotoday.com/clinical-trials/prostate-cancer/93644-a-randomized-controlled-trial-of-transcutaneous-oestrogen-patches-versus-lhrh-agonists-in-prostate-cancer-2.html

ASCO 2017: How Randomized Trials of STAMPEDE Have Influenced Treatment Decisions in the United Kingdom
Click on Our Link to read more - STAMPEDE
or Go To
https://www.urotoday.com/conference-highlights/asco-2017/asco-2017-prostate-cancer/96343-asco-2017-how-randomized-trials-of-stampede-have-influenced-treatment-decisions-in-the-united-kingdom.html

The Local Experience by one of Our Own
(with Ketoconozole and Estrogen patches)
I was diagnosed at age 50 in 1999 with a Gleason of 3+3 and had surgery to remove the prostate.
Click on Our Link to read more - Our Own
or Go To
http://rvaprostatecancersupport.org/Our Own.pdf
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Article:

Lipid catabolism inhibition sensitizes prostate cancer cells to antiandrogen blockade.
On This Site You will find:

Prostate cancer (PCa) is the most common malignancy among Western men and the second leading-cause
of cancer related deaths. For men who develop metastatic castration resistant PCa (mCRPC), survival is
limited, making the identification of novel therapies for mCRPC critical.

Click on Our Link to read more
Lipid Catabolism
or go to:
https://www.urotoday.com/recent-abstracts/urologic-oncology/prostate-cancer/95534-lipid-catabolism-inhibition-sensitizes-prostate-cancer-cells-to-antiandrogen-blockade.html
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Article:

Advanced Prostate Cancer Consensus Conference: APCCC
On This Site You will find:

Articles - Video Lectures - Clinical Trials -Centers of Excellence - Conference Highlights - Journal - Calendar

Click on Our Link to read more
Conference
or go to:
https://www.urotoday.com/video-lectures/advanced-prostate-cancer-consensus-conference-apccc.html?utm_source=newsletter_4444&utm_medium=email&utm_campaign=advanced-prostate-cancer-consensus-conference-interviews-with-presenters-by-alicia-morgans-neal-shore-and-charles-ryan
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Article:

PCa Commentary Vol. #105: FOLLICLE STIMULATING HORMONE (FSH): Its Suppression by Degarelix (Firmagon)
May Contribute to the Drug’s Effectiveness in Androgen Suppression and Its Lesser Cardiotoxicity Compared to Leuprolide (Lupron.)
FOLLICLE STIMULATING HORMONE
or go to:
http://www.pctrf.org/pca-commentary-vol-105-follicle-stimulating-hormone-fsh-suppression-degarelix-firmagon-may-contribute-drugs-effectiveness-androgen-suppression-lesser-cardioto/
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Article:

Clinical comparison of the efficacy of three different bowel preparation methods on the infectious
complications following transrectal ultrasonography guided prostate biopsy in nursing practice.
Click on Our Link to read more
Infection
or go to:
https://www.ncbi.nlm.nih.gov/pubmed/28401738
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Article:

Dosimetric impacts of endorectal balloon in CyberKnife stereotactic body radiation therapy
(SBRT) for early-stage prostate cancer.
Click on Our Link to read more
CyberKnife
or go to:
https://www.ncbi.nlm.nih.gov/pubmed/28407345
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PAN Foundation

The copay assistance program for individuals with metastatic prostate cancer has just opened at the Patient
Access Network (PAN) Foundation. This is a great potential opportunity for eligible men affected by metastatic
prostate cancer to receive up to $12,000 a year in financial assistance.

For more information visit:

Click on Our Link to read more

PAN

or go to:
http://bit.ly/2n1SftA

You may apply online or call 1-866-316-7263.

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