The State of Bipolar Androgen Therapy in Prostate Cancer - Emmanuel Antonarakis

[cigafred]

A phlosophical overview. My favorite comment: "My comfort with off study BAT is increasing over time, my personal comfort" although he, as always, prefers to stay in the CR setting.

[Tall_Allen]

" The lessons are that there are certain patients that you should not give this to. The concern is that you may cause a disease flare, because while in 30% to 40% of people, you see a benefit, in 50% you see a neutral effect, in 10% you do see a disease flare. And this is important for anyone in the community thinking about using this." I would stick to closely watching it in a clinical trial. Patients have to understand the risks.

[Hidden in reply to Tall_Allen]

How do you know who these people will be, beforehand?

[Tall_Allen in reply to Hidden]

Good question! You don't! That is why BAT has so far failed to catch on -- they have not been able to find a predictor of success or failure. And Antonarakis is a master of genomics and proteomics and has searched hard.

[pjoshea13]

Thanks for posting!

The early interjections from Charles Ryan were amusing, I thought. He seemed less than impressed by a few things - for instance, that testosterone caused a reduction in AR (androgen receptor) protein. He called it "unamplification". I believe that this was demonstrated in cell studies years ago. When PCa cells are starved of testosterone [T], you get AR amplification. Increase T levels & the need for additional AR disappears and AR levels drop.

Eventually, Ryan pointed out the obvious - that BAT simply reverses some of the changes caused by ADT. Which suggests to me that BAT might be most useful when ADT-induced adaptations can still be reversed. CRPC can occur at any time. For most men on classic ADT, CRPC occurs within 18-24 months, but it can occur in less than 12 months. I am inclined to think that BAT should start 3 months after ADT.

T is a ligand for the AR, but not for AR splice variants that have lost the section that T binds to. So, no point in waiting for splice variants to emerge IMO.

Regarding MYC:

"In cancer, c-myc is often constitutively (persistently) expressed. This leads to the increased expression of many genes, some of which are involved in cell proliferation, contributing to the formation of cancer." [1]

From an old German study [2]:

"MYC gene "amplifications" were present before ADT in ... 33% of the cases ..; the frequency of these "amplifications" increased to ... 57% after ADT."

So, the news that BAT caused a reduction in MYC protein & trancriptions wasn't surprising.

{Note, the mention of "Ki-67", which is a key proliferation marker [3]. Not mentioned much in posts, but over 1,000 hits on PubMed for <prostate "Ki-67">. There would be much loss of sleep if we all new our Ki-67 number. (a grim lol)}

-Patrick

[1] en.wikipedia.org/wiki/Myc

[2] pubmed.ncbi.nlm.nih.gov/110...

[3] en.wikipedia.org/wiki/Ki-67...

[EdBar]

Thank you for the video, all of his comments regarding who is a candidate and knowing whether it is working for a patient in 3 months lines up with everything Dr. Sartor explained to me. Sartor was very involved in the TRANSFORMER trial. And they didn’t even get into a discussion about how it may resensitize you to Xtandi once the BAT stops working as another benefit. The QOL aspects together with it being effective for 35-40% of castrate resistant men is outstanding when compared to any other treatment. I will be using this treatment off study when and if the time comes, already discussed with Sartor.

Ed

[cigafred in reply to EdBar]

Thanks Ed. I did have a couple of appointments with Dr. Barata, who I think is #2 to Dr. Sartor and a PI in his own right, prior to starting my own BAT experiments.

[EdBar in reply to cigafred]

Yes Pedro is also excellent, he’s done some pre screening on me a couple of times before the “big dog” came in. He no longer does that - he has his own group of patients and really knows his stuff too.

Ed

[cigafred in reply to EdBar]

Totally agree--outstanding doctor as far as this layman can tell.

[cigafred]

I was just asking for BAT guidance.

[Justfor_]

Emmanuel Antonarakis: "There is a second idea, which is even more intriguing but remains to be proven. And that is... You are familiar with the concept of lineage plasticity, where an AR-positive or addicted cell over time, under the influence of hormonal therapy pressures, becomes more AR indifferent or less AR sensitive."

Greek minds, from entirely different perspectives, think alike:

Strength of materials elementary knowledge: Stress steel, or any elastic material, beyond its yield point and "plastic" deformation before final rapture will follow. That is the reason for which I have elected (to try) to keep my cancerous cells within their "elastic" range.

healthunlocked.com/prostate...