Very low testosterone & fast rising PSA

[Advo__cate]

I’m not sure how to ask my question but will throw this out there - my husband is AR-v7 positive (1 out of five is positive), Today PSA is 44, up from 19 last month. Testosterone was 44 last month and is 2.5 this month. MO was convinced the Testosterone wold be well over 50 and feeding the cancer. So, what’s feeding the cancer if T is so low?

[Tall_Allen]

Unfortunately, the cancer eventually evolves to the point that it does not need anything extraneous to feed it - it feeds itself. It evolves many ADT resistance mechanisms like translocating the androgen receptor (AR) to the nucleus and manufacturing its own androgens internally, which makes it impervious to outside interference with ADT. It also upgrades the AR, making so many copies that even the slightest amount of androgen activates it (which is why ADT has to continue). It also evolves to get activated by strange substances, like bicalutamide.

AR-V7 is just one of many changes that prostate cancer may undergo as it evolves. It means the androgen receptor no longer needs testosterone or any other androgen to stimulate growth of the cancer. There have been some very small trials of using chemo or high dose testosterone (BAT) to reverse AR-V7, which have been variably effective. There is a clinical trial of using niclosamide for this purpose. But AR-V7 is just one resistance mechanism. Other ADT resistance mechanisms are being targeted in trials by indomethacin, and other substances. Here is a run-down of substances under investigation:

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

[Advo__cate in reply to Tall_Allen]

Thank you. I asked the oncologist about investigational therapies but we moved on to another subject before getting back to my question. We have to be cleared by a cardiologist here at the cancer center to begin taxotere next week. Thankfully, the oncologist has agreed to a lower dose due the cardiac risk. He has ordered further genomic testing, we won’t get the results for another 4-6 weeks though.

I’ll ask him about BAT and the other things.

[pjoshea13]

The androgen receptor [AR] splice variant AR-V7 lacks the domain that testosterone [T] binds to, but it is able to funtion as though it were normal AR following T binding.

-Patrick

[pjoshea13 in reply to pjoshea13]

It has been suggested that T restoration might resensitize AR-V7 related CRPC to ADT.

-Patrick

[Advo__cate in reply to pjoshea13]

Thanks! will for sure bring it up to the MO.

[tango65]

You could consider looking into the clinical trials for niclosamide and anti androgens. The trials are done at UC Davis near Sacramento:

clinicaltrials.gov/ct2/resu...

Niclosamide could "neutralize" the AR-V7.

ncbi.nlm.nih.gov/pubmed/247...