A look at the next generation of Andr... - Fight Prostate Ca...

Fight Prostate Cancer

2,788 members1,018 posts

A look at the next generation of Androgen Receptor therapies--AR Degraders/PROTACS

NPfisherman profile image
10 Replies

Greetings FPC members,

Recently, Cujoe the K9 Wonder asked me if ARV-110 might deserve a post and I confirmed that the next generation of AR drugs--the PROTACs / AR Degraders indeed deserve a serious look. What does one do when those second line AR drugs like abiraterone, TAK-700, enzalutamide, apalutamide, or darolutamide stop working.?? Today, people turn to things like Provenge, Xofigo, Lu-177 or Cabazitaxel, but in the future, these kind of drugs will be the answer also.

But... what is a PROTAC /AR Degrader?? A PROTAC causes breakdown of proteins by targeting a specific system (in this case--AR system in PCa cell lines) as opposed to being an androgen production blocker (abiraterone) or an AR binder inhibitor (enzalutamide). An explanation of PROTAC below:

en.wikipedia.org/wiki/Prote...

But why should this be any better than those second generation drugs ?? My response to you is that these drugs by degrading the AR receptor in prostate cancer cells have a greater ability to inhibit the wild AR type mutations and hold them in check, thus stopping progression or causing regression and buying time, especially for heavily treated patients. ( Our goals--QOL and Buying Time !!!)

ARV-110 is one of the AR Degraders and is already into Phase 2 trials. Some information about ARV-110 from Arvinas:

arvinas.com/pipeline-progra...

and the initial data release from Phase 1 trial:

ir.arvinas.com/news-release...

There are a number of AR Degraders in development currently and I have listed some information on the ones that I have found.

ARD-69

pubs.acs.org/doi/abs/10.102...

MTX-23

mct.aacrjournals.org/conten...

UT-34

clincancerres.aacrjournals....

With ARV-110 in Phase 2 trials, and bromodomain inhibitors like ZEN-3694 and CCS-1477in Phase 2 or headed into Phase 3, we should see some new classes of drugs on the treatment scene within 5 years. These will be added on in combo with other drugs and add years to PCa sufferers lives..

The Science is Coming !!! so keep them peepers open folks...

Don Pescado

Written by
NPfisherman profile image
NPfisherman
To view profiles and participate in discussions please or .
Read more about...
10 Replies
hansjd profile image
hansjd

Dear Fish once again thanks so much for your ongoing research and your great posts. Peepers are definitely open. Lol G&J

NPfisherman profile image
NPfisherman in reply to hansjd

Glad you liked it... AR Degraders and bromodomain inhibitors will be game changers for PCa, especially for the heavily treated... there is a clinical trial now with Enzalutamide, ZEN 3694 and Keytruda at UCSF... an AR blocker, a bromodomain inhibitor, and a checkpoint inhibitor for MCRPC... combos... see below:

clinicaltrials.gov/ct2/show...

It is how overall survival will be changed... when I was diagnosed Stage 4 in 2018, the American Cancer Society said I had a 20% chance of surviving 5 years... (their statistics always lag behind)....recently, I saw another agency said 33%...

With other treatment trials like BAT, nanoparticles, CAR-T, BiTE, vaccines, and more, there is real hope for all of us...

Fish

Hope59 profile image
Hope59

Great post, Fish!

NPfisherman profile image
NPfisherman in reply to Hope59

Thank you.... like everyone here, I am grateful for all the research that is going on and I try and do justice to the discoveries that will benefit so many...

Fish

GreenStreet profile image
GreenStreet

Great post. Thanks for all the research you bring to the site.👍

NPfisherman profile image
NPfisherman in reply to GreenStreet

You're welcome... I find the science fascinating.... ARV-110 will be a game changer for many and add years to lives... because it is a new class of drugs that addresses the problem of MCRPC, I believe it will be approved faster...

Fish

TheTopBanana profile image
TheTopBanana

Thank you 🌹🌹🌹

NPfisherman profile image
NPfisherman in reply to TheTopBanana

You're welcome... the science just keeps on happening... BTW, love the Kermit picture....it ain't easy being green....LOL....

Fish

TheTopBanana profile image
TheTopBanana in reply to NPfisherman

Do you think it could be useful for hormone sensitive patients?

NPfisherman profile image
NPfisherman in reply to TheTopBanana

I believe it could, but at this point, we have a study showing increased efficacy with the apalutamide and abiraterone combo... IMHO, it should be held for the castrate resistant crowd initially...

Fish

You may also like...

Androgen Receptor Activity (ARA) for BAT

suggestions? Androgen receptor activity in prostate cancer dictates efficacy of bipolar androgen...

Efficacy and safety of BAT in CRPC following Abi or Enza resistance: A systematic review

some patients' sensitivity to drugs such as abiraterone (Abi) and enzalutamide (Enz). ... \\"In a...

A Reason why Checkpoint Inhibitors may not be effective has been found...

protein receptor led to decreased responsiveness to Checkpoint Inhibitors... RIG-I is a receptor...

The Take Home Message on Cujoe's Posting on CRISPR edited T cells--THIS IS HUGE AND IMPORTANT

-tumors-now-tested-on-patients-phase-i-ii-trial-to-begin Could a drug like CpG be added to these...