Androgen Receptor Activity (ARA) for BAT

[cigafred]

I read somewhere (here?) that ARA is a good predictor of BAT efficacy and that Johns Hopkins has a test for it. I have been trying to track down such a test, at Johns Hopkins or elsewhere, with no success. Any suggestions?

Androgen receptor activity in prostate cancer dictates efficacy of bipolar androgen therapy through MYC This work identifies high AR activity as a predictive biomarker of response to BAT and supports a treatment paradigm for prostate cancer involving alternating between AR inhibition and activation. ncbi.nlm.nih.gov/pmc/articl...

The AR activity of a metastasis sample was defined by its relative expression levels of genes predefined to be associated with canonical AR activity; AR, FOXA1, HOXB13, KLK2, KLK3, NKX3-1, STEAP2, and TMPRSS2, as previously described [9]. 9. Ylitalo EB, Thysell E, Jernberg E, Lundholm M, Crnalic S, Egevad L, et al. Subgroups of castration-resistant prostate cancer bone metastases defined through an inverse relationship between androgen receptor activity and immune response. Eur Urol. 2017;71:776–87.

[KocoPr]

It looks like they determined AR activity based on a somatic mutation. In my case and 50% of advanced PCa have the TMPRSS2/ERG FUSION.

so if you have one of those mutations and you’re not castrate resistant (MYC high), nor bone mets then you could do a test with testosterone propianate for a week. You can buy tests cheap at ultalabs/quest diagnostics to monitor.

As a side note: Covid19 uses TMPRSS2/ERG Fusion to enter cells along with testosterone.

Covid-19 pathogenesis in prostatic cancer and TMPRSS2-ERG regulatory genetic pathway

ncbi.nlm.nih.gov/pmc/articl...

[cigafred in reply to KocoPr]

Thank you. Some time back I did 6 rounds with T-cyp, but it seemed not to be working. Before I try again I am gathering info.

[KocoPr in reply to cigafred]

Do you have any tumors they can biopsy to check recent mutations and MYC levels?

The problem with t-cyp is it takes a month to get it out of your system and it isn't a sharp drop off.

Are you using daro or enzalutimide?

You could try a rapid BAT with propianate

[cigafred in reply to KocoPr]

No tumors, on Eligard and undetectable for many years except during BAT and most recent PSA 0.02. Not going to try BAT again until I think I have found a likely way.

[Ramp7 in reply to KocoPr]

Agreed, presently I am doing just that, rapid T "Propionate" then two days of Daro. Let it wash out, repeat. A couple of months ago I tried one infusion of Cypionate. It took 6 weeks for my T to drop under 100, too slow a decline I feel.

[KocoPr in reply to Ramp7]

How long is your daro washout before initiation of another high T for each rapid BAT?

On pBAT I give daro 5 days to washout.

[Ramp7 in reply to KocoPr]

We are following the same course. Five days.

[KocoPr in reply to Ramp7]

How do/did you like the rapid BAT? What was your PSA before and after?

I am curious why you decided to do rBat

[Ramp7 in reply to KocoPr]

My initial pBAT results were positive. After 6 months PSA not responding as well to the cycles. Denmeade commented still stable. A PSMA scan showed L3 as a hot spot so I had radiation to that. Completed about 10 days ago. PSA came down from 25 to 20. I shall monitor over the next few weeks. Denmeade suggested 2 to 3 months of Darlutamide. I wanted to try rBAT first.

[KocoPr in reply to Ramp7]

I think rBAT pr pBAT would work synergistically with radiation therapy.

So when you started pBAT what was your PSA? Im curious because your PSA climbed to 25 under pBAT?

I seem to be a long way from that level of PSA. I am bouncing around the 0.1 range wjere i started at 0.02.

I know I need to keep the beast fed and happy on T so i am not concerned yet. I know and have stayed on daro for an extra week to lower my PSA and it worked great so I know i can do that to reduce my PSA .

[PCaWarrior in reply to KocoPr]

Theoretically rBAT should work better than pBAT with SBRT or RT. We don't have any data though (unless you count me).

[cigafred]

This answer I got from a moderator on a PCa Facebook group might be of interest.

"A std PCR test showing mRNA from the exosomes will reveal the level of AR-FL and AR-V7. A very high AR-FL is a good predictor for response to BAT. Normally a high FL is accompanied by a high AR-V7 and other splice variants. My MO at the hospital draws separate blood for this tests, we are using the results for deciding when to initiate BAT and the ARSi. After the last Testo injection AR-V7 was reduced to zero."

[MateoBeach in reply to cigafred]

You have a very progressive MO with that. Congratulations on the zero AR-V7.

AR activity cycling and the inverse relationship to MYC can now be recognized as at least part of the mechanism for BAT efficacy. Others being Darwinian competition between AR+/AR- populations and DNA DSBs.

[cigafred in reply to MateoBeach]

Not me, the moderator (the site forces us to use real names, so I do not use the name here without permission). But good information, thank you.

[PCaWarrior in reply to MateoBeach]

I wish I could write as succinctly as you do. Seriously.

I aways end up overly verbose and use 2 bit words. Mark of stupidity is what I tell my son.

[cigafred in reply to PCaWarrior]

Thank you. Now, if only I had something to say . . . .