Quercetin & AR-V7.

[pjoshea13]

New study below [1].

A common form of resistance to Xtandi & Zytiga is the emergence of androgen receptor [AR] splice variant AR-V7, which retains AR functionality but does not need androgen for activation.

"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."

Seems prudent to use quercetin while on Xtandi or Zytiga, etc.

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/287...

Mol Cancer Ther. 2017 Jul 20. pii: molcanther.0030.2017. doi: 10.1158/1535-7163.MCT-17-0030. [Epub ahead of print]

Quercetin targets hnRNPA1 to overcome enzalutamide resistance in prostate cancer cells.

Tummala R1, Lou W1, Gao AC1, Nadiminty N2.

Author information

1

Department of Urology, University of California Davis.

2

Department of Urology, University of Toledo [e-mail].

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 anti-androgen, 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 anti-androgen therapy.

Copyright ©2017, American Association for Cancer Research.

PMID: 28729398 DOI: 10.1158/1535-7163.MCT-17-0030

[Neal-Snyder]

Hi Patrick,

Thanks very much for this. Is there any indication of what might be an appropriate dose? Thanks again.

Neal

[pjoshea13 in reply to Neal-Snyder]

Hi Neal,

I seem to have neglected quercetin in my "Foods/Supplements-Vitamins:" series.

I don't recall that bioavailability is an issue, or side effects. I would use a high dose in the context of my post. What might that be? 2-3 high-strength caps 3 times daily? A guess. I will try to do better.

-Patrick

[Dan59]

Thank You Patrick, I am going to get some quercetin and start taking it in anticipation of taking a chemo break and going back on xtandi. Nothing I would like better than to reuse zytiga and xtandi.

It would seem prudent for those on xtandi and zytiga to be supplementing with quercetin

Dan

[Thinus]

Thanks for the info, already using Quercitin in Combination with Green Tea Extract (concetrated). Not yet on Casodex or Xtandi, just Lucrin.

[Dan59]

Thanks Joel, I found a study from pub med on niclosamide overcoming xtandi resistance , I have printed it and will bring it to my MO this week.

Dan

[ctarleton in reply to Dan59]

This is interesting, too.

www3.epa.gov/pesticides/che...

[pjoshea13 in reply to ctarleton]

Scott Pruitt wouldn't let me in. -Patrick

[GeorgeGlass in reply to ctarleton]

what was the conclusion of this article? I couldn't open it.

[ctarleton in reply to GeorgeGlass]

It was a 9 page US EPA Pesticides Fact Sheet for Niclosamide, document # EPA-738-F99-013, dating from 1999, when Niclosamide had been used for poisoning lampreys and snails in the Great Lakes area. Impacts on humans and water quality were also mentioned.

www3.epa.gov/pesticides/che...

[GeorgeGlass in reply to ctarleton]

oh ok, thanks. Pesticides just about everywhere and very little being done to stop it