List of new drugs to overcome resistance

[snoraste]

Does anyone has a list of drugs that are under investigation to overcome resistance to ADT/Abi/Doc etc?

[GP24]

You can remove the resistant tumor tissue using radiation:

pubmed.ncbi.nlm.nih.gov/305...

[snoraste]

Thanks Nal. That is in fact the plan. I'm told by my MO that the two PARPi you mentioned got FDA approval for my case. He just wants to see ow far I go with Abi without additional intervention. Jury is out there. He's also open to adding a PD1/PDL1 agent to PARPs, but wants to monitor the progress of the clinical trials for another few months. Interestingly, they are working on a Thorium227 therapy with a new ligand (not PSMA) that he was very happy about.

[Tall_Allen]

Sometimes chemo will reverse resistance to Zytiga or Xtandi. They hope that BAT might. Some of the new hormone therapies (Erleada and Nubiqa) inhibit AR proliferation and may extend the usefulness of ADT. Carboplatin and PARP inhibitors seem to be effective in similar situations and may extend the usefulness of taxane therapy.

[snoraste in reply to Tall_Allen]

Thanks Allen. I thought there were a few drugs on trial specifically for overcoming resistance, similar to Onvarsertib (targetedonc.com/view/onvans... . My MO also thinks PARPi would achieve similar results.

[Tall_Allen in reply to snoraste]

Looks good so far. I think the two trials at UCDavis on niclosamide are also to determine if it helps Zytiga or Xtandi work better.

[rassusukumaran in reply to Tall_Allen]

Hai Allen, I have been following your well-informed advice and comments for years now. Your comment above "new hormone therapies (Erlada and Nubiqa) inhibit AR proliferation and extend usefulness of ADT" drew my attention. Iam MCRPC and failed Zytiga with PSA of 16.5 and was put on Apalutamide by an oncologistfor 2 months and PSA shot up to 52. He has since advised me to stop the drug. What do you think happened in this context

[Tall_Allen in reply to rassusukumaran]

It sounds like you are cross-resistant

[rassusukumaran in reply to Tall_Allen]

Thank you Allen for the reply. Does it mean any of the new drugs including Enza will not work in my case even if I added Indomathasin or Chemo to knockdown AR resistance. So what are my options at this point if you do not mind.

[Tall_Allen in reply to rassusukumaran]

Probably the approved anti-androgens won't work, at least not for long. You can try to rechallenge after Chemo - sometimes it helps.

[snoraste]

I think this is trial he was talking about:

clinicaltrials.gov/ct2/show...

[GeorgeGlass]

Are you currently castrate resistant, with rising psa on adt alone?

[snoraste in reply to GeorgeGlass]

I’m still hormone sensitive. Been on intermittent Abi/ADT.

[GeorgeGlass in reply to snoraste]

How are you doing with regards to the side effects? How much prednisone do you take with it?

[snoraste]

I'm on 10mg a day. Side effects are mainly fatigue, but I exercise aggressively and that helps a great deal.