New cell study below [1].
Treatment resistance begins on day 1 of treatment. Cells under attack have a variety of survival strategies to fall back on. Activation of the the PI3K/Akt/mTOR pathway is fairly common [2].
I have long wondered why PCa drugs don't come paired with drugs to inhibit resistance. After all, if one could extend the life of a drug by a mere year, that would translate into a big bonus boost for BigPharma fat cats.
{My primary interest in phytochemical supplements is due to the possibility of inhibiting cell survival pathways.}
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From the study:
"We previously found that a GLP-1 {Glucagon-like peptide 1} analog, exendin-4 (Ex-4), inhibited the growth of prostate cancer cells through suppressing the PI3K/Akt/mTOR pathway, which is activated in response to enzalutamide treatment and reported to be closely related to resistance to enzalutamide."
"Our study demonstrated that exendin-4 alleviated resistance to enzalutamide, and suggested that exendin-4 combined with enzalutamide may be a more efficacious treatment for patients with advanced prostate cancer."
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"Exenatide (synthetic exendin-4), glucagon-like peptide-1 (GLP-1), and GLP-1 analogues have actions with the potential to significantly improve glycemic control in patients with diabetes." [3]
"Exenatide, sold under the brand name Byetta and Bydureon among others, is a medication used to treat diabetes mellitus type 2. ... It is a less preferred treatment option after metformin and sulfonylureas." [4]
Byetta might be a nice fit for men on Enzalutamide. IMO
-Patrick
[1] ncbi.nlm.nih.gov/pubmed/319...
Prostate. 2020 Jan 22. doi: 10.1002/pros.23951. [Epub ahead of print]
Exendin-4 enhances the sensitivity of prostate cancer to enzalutamide by targeting Akt activation.
Wenjing H1, Shao Y2, Yu Y2, Huang W2, Feng G2, Li J2.
Author information
Abstract
BACKGROUND:
Glucagon-like peptide 1 (GLP-1) and its analogs are first-line choices for the treatment of type 2 diabetes mellitus. Recent studies have shown that they exhibit antitumor properties in some tumors. We previously found that a GLP-1 analog, exendin-4 (Ex-4), inhibited the growth of prostate cancer cells through suppressing the PI3K/Akt/mTOR pathway, which is activated in response to enzalutamide treatment and reported to be closely related to resistance to enzalutamide. So we speculated that exendin-4 may enhance the sensitivity of prostate cancer to enzalutamide through inhibiting Akt activation.
METHODS:
LNCap and CWR22RV1 cell lines, as well as mice bearing xenografts formed from the two cells, were used.
RESULTS:
Exendin-4 in combination with enzalutamide dramatically suppressed tumor growth of prostate cancer cells compared to enzalutamide alone; exendin-4 is capable of antagonizing enzalutamide-induced invasion and migration of both prostate cancer cells (P < .05). Furthermore, the combination treatment significantly reduced Akt and mTOR levels that were triggered by enzalutamide administration, caused a further decrease in nuclear AR localization compared with the enzalutamide as a monotherapy (P < .5), though exendin-4 treatment alone showed no effect on nuclear AR.
CONCLUSION:
Our study demonstrated that exendin-4 alleviated resistance to enzalutamide, and suggested that exendin-4 combined with enzalutamide may be a more efficacious treatment for patients with advanced prostate cancer.
© 2020 Wiley Periodicals, Inc.
KEYWORDS:
enzalutamide; exendin-4; prostate cancer; sensitivity
PMID: 31967357 DOI: 10.1002/pros.23951
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[2] en.wikipedia.org/wiki/PI3K/...
