Bipolar Androgen Therapy for mPCA

[snoraste]

I’m not sure if Patrick shared this article with us or not (most likely the answer is yes). But just in case here it is:

practiceupdate.com/c/62093/...

[John-carp]

Hello

While I am not castrate resistant I will be taking a vacation after 18 months of ADT. Makes me nervous but the MD thinks it wise

[Hidden in reply to John-carp]

metastatic?

[snoraste]

Were you diagnosed as stage 4? Curious why he's taking you off HT.

[John-carp in reply to snoraste]

Hi. Ya. Stage IV. My PSA is undectectable after these months so they feel it’s a safe move. We will monitor and Jump back on if PSA moves

[John-carp in reply to snoraste]

Hi. Yes. Stage IV. Mets to lymph nodes. PSA .89 after RP. HT working keeping PSA down. I am UCSF and going to get second opinion at Seattle cancer care. Low risk to go off and see

[BigRich]

Thank you for the information.

Rich

[Pwjpp55]

I recently transferred to the U of Minnesota clinic. I've been sliced and burned, but still have PC. I just reached the 18 month on ADT point and my oncologist also recommend a break and a recheck in 3 months, which I agreed to try.

Another adventure in healthcare!

[John-carp in reply to Pwjpp55]

Let’s do it!!!

[Stegosaurus37]

It's a bit difficult for this lay person to figure out what is going on here. Except that it seems to work. It seems to be flood the tumor/lesions with far, far more food than they can handle followed by starvation. This one-two punching wears down the tumor's vitality knocking it back.

Am I totally misconstruing this?

[snoraste in reply to Stegosaurus37]

pccncalgary.org/n_bipolar.pdf

From wpopomaronis in the posts. Nice slides

[Stegosaurus37 in reply to snoraste]

Thanks!! I understand it a lot better now. I'm on my first round of docetaxel so I would be excluded from this anyway.

[Hidden in reply to snoraste]

regarding the diagram in the PDF:

The Androgen Receptor is more like a shortstop (with a glove) rather than just the glove. Once the shortstop catches the ball, he runs to second base (the nucleus) where he does something (expresses proteins) and then throws the ball to first (and the proteins do something else). The pair (androgen, androgen receptor) are the signalling part of the story, but the signal causes other things to happen, and that is why the signal is important. If the signal caused nothing to happen, no one would care about the signal.

[Hidden in reply to Stegosaurus37]

Misconstruing, yes, a little. The purposes of BAT it to resensitize the cancer to enzalutimide. Since the conceptual reason that enza (hormone therapy) fails is the ARv7 variant (that has no hormone binding domain), BAT is aimed at weakening the ARv7 population, rather than being aimed at (weakening) the across-the-board prostate cancer population, for which population testosterone IS considered by some as "food", ie a growth promoter.

"It seems to work" is the key take-away, in some people, and for some time.

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addition 12/27

The neuroendocrine variation is also a reason that hormone therapy could fail, and is becoming more prevalent, as a component, after 2nd line (abi/enza) treatment. Snuffy mentions this around 3:25. I meant o post the "Grand Rounds" video he mentions, where he goes into this more.

youtu.be/IgMxwo2itrQ?t=3m25s(Not working as expected?)

This is my understanding at least. I do hear people say that the AR can interfere with "licensing" during the duplication of the cell nucleus (Isaacs is the person, at Johns Hopkins), but I don't undertand that mechanism at all, since gene expression is so different from cell replication.

[snoraste]

That’s great - hoping for a complete remission for you.