Nuclear Receptor ERRα Contributes to Castration-Resistant Growth of Prostate Cancer via Its Regulation of Intratumoral Androgen Biosynthesis

[pjoshea13]

New paper below [1].

The paper describes how PCa can become resistant to classic ADT by making androgen from scratch. (The reason some use a statin &/or Avodart.)

Note. ERRα is: estrogen-related receptor alpha.

"ERRα exhibited an increased expression in metastatic CRPC"

It "could act to promote castration-resistant growth via direct transactivation of two key androgen synthesis enzymes CYP11A1 and AKR1C3, and hence enhance intraprostatic production of dihydrotestosterone (DHT) and activation of AR signaling in prostate cancer cells."

CYP11A1is involved in the conversion of cholesterol to pregnenolone. It is limited, of course, by the amount of cholesterol in the cell. Hence, a reason for using a statin while on ADT.

[2]: "Aldo-keto reductase family 1 member C3 (AKR1C3) is a steroidogenic enzyme that plays a crucial role in the conversion of adrenal androgen dehydroepiandrosterone (DHEA) into high-affinity ligands for the androgen receptor (testosterone [T] and dihydrotestosterone [DHT])."

[3] "The antiandrogen therapeutics apalutamide and darolutamide entered the clinic in 2018 and 2019, respectively, for the treatment of castration-resistant prostate cancer (CRPC). Increased expression of the enzyme aldo-keto reductase 1C3 (AKR1C3) is phenotypic of CRPC. The enzyme acts to circumvent castration by producing potent androgens that drive proliferation. Furthermore, AKR1C3 mediates chemotherapeutic resistance to the standard of care, enzalutamide, a structural analogue of apalutamide. Resistance develops in almost all CRPC patients within three months of beginning treatment. Herein, we report that both apalutamide and the structurally distinct darolutamide induce AKR1C3 expression in in vitro models of prostate cancer and are susceptible to AKR1C3-mediated resistance."

The possibility of backdoor production of DHT is a reason to consider Avodart.

-Patrick

[1] pubmed.ncbi.nlm.nih.gov/322...

[2] pubmed.ncbi.nlm.nih.gov/231...

[3] pubmed.ncbi.nlm.nih.gov/321...

[j-o-h-n]

What the hell do they know.?... They're only doctors.............

Good Luck, Good Health and Good Humor.

j-o-h-n Wednesday 04/01/2020 2:06 PM DST

[monte1111 in reply to j-o-h-n]

My dr. stayed as far away from me as she could, in the tiny room we were in. I so much wanted to give her a great big thank you hug, and plant a sloppy one right on her lips ... and watch her go screaming down the hall.

[j-o-h-n in reply to monte1111]

With or without your mask?

Good Luck, Good Health and Good Humor.

j-o-h-n Wednesday 04/01/2020 8:10 PM DST

[monte1111 in reply to j-o-h-n]

It is so tempting to knock off a bank right now. Everyone wearing masks. Remember, you heard it here first. Don't try to like this --- apparently, I am on the Do Not Like list.

[j-o-h-n in reply to monte1111]

I already did stick up a bank.....it's the bank where you deposit a toaster and they give you three thousand dollars.....

One day I'll let you know a great plan to stick up a bank......

Good Luck, Good Health and Good Humor.

j-o-h-n Wednesday 04/01/2020 10:31 PM DST