Natural killer cells suppress enzalutamide resistance and cell invasion in CRPC via targeting ARv7.

[pjoshea13]

New study below [1].

"Despite the success of androgen-deprivation therapy (ADT) with the newly developed anti-androgen enzalutamide (Enz, also known as MDV3100) to suppress castration resistant prostate cancer (CRPC) in extending patient survival by an extra 4.8 months ..."

Resistance is often associated with the ARv7 androgen receptor mutation.

"Here we identify an unrecognized role of Natural Killer (NK) cells in the prostate tumor microenvironment that can be better recruited to the CRPC cells to suppress ARv7 expression resulting in suppressing the Enz resistant CRPC cell growth and invasion."

Something to bear in mind for those using estradiol for ADT (or even DES) - estrogen reduces the NK population.

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/283...

Cancer Lett. 2017 Mar 31. pii: S0304-3835(17)30217-3. doi: 10.1016/j.canlet.2017.03.035. [Epub ahead of print]

Natural killer cells suppress enzalutamide resistance and cell invasion in the castration resistant prostate cancer via targeting the androgen receptor splicing variant 7 (ARv7).

Lin SJ1, Chou FJ1, Li L2, Lin CY1, Yeh S1, Chang C3.

Author information

Abstract

Despite the success of androgen-deprivation therapy (ADT) with the newly developed anti-androgen enzalutamide (Enz, also known as MDV3100) to suppress castration resistant prostate cancer (CRPC) in extending patient survival by an extra 4.8 months, eventually patients die with the development of Enz resistance that may involve the induction of the androgen receptor (AR) splicing variant ARv7. Here we identify an unrecognized role of Natural Killer (NK) cells in the prostate tumor microenvironment that can be better recruited to the CRPC cells to suppress ARv7 expression resulting in suppressing the Enz resistant CRPC cell growth and invasion. Mechanism dissection revealed that CRPC cells compared to normal prostate epithelial cells could recruit more NK cells that might then lead to alterations of the microRNA-34 and microRNA-449 to suppress both ARv7 expression and ARv7-induced EZH2 expression to suppress CRPC cell invasion. Together, these results identify a new potential therapy using recruited NK cells to better suppress the Enz resistance and cell invasion in CRPC at the later enzalutamide resistant stage.

Copyright © 2017 Elsevier B.V. All rights reserved.

KEYWORDS:

ARv7; Enzalutamide; Natural Killer cells

PMID: 28373004 DOI: 10.1016/j.canlet.2017.03.035

[BigRich]

"Mechanism dissection revealed that CRPC cells compared to normal prostate epithelial cells could recruit more NK cells that might then lead to alterations of the microRNA-34 and microRNA-449 to suppress both ARv7 expression and ARv7-induced EZH2 expression to suppress CRPC cell invasion." How would this be done?

Rich

[pjoshea13 in reply to BigRich]

You would want to promote healthy levels of NK cells.

Scroll to "Natural Ways to Increase Natural Killer Cells":

selfhacked.com/2016/04/15/i...

Importantly, IMO, avoid estrogen-driven ADT.

-Patrick

[BigRich in reply to pjoshea13]

Thank you for the information.

Rich

[Dan59 in reply to pjoshea13]

This is a great paper on ways to increase NK cells

[Dan59]

Great Paper Patrick, Interesting to note that estrogen therapy reduces natural killer cells. I printed the paper from pubmed, for my Oncologist to see, as ideally after chemo it would be great to return to xtandi with a boost to the NK. .