PARP Inhibitors.

[pjoshea13]

Brief update on PARP Inhibitor trials:

targetedonc.com/videos/clin...

{PARP is involved in DNA repair. The idea behind inhibition is that PCa cells that have DNA repair defects may depend on PARP for viability.

Some defects are inherited, but resistance to Zytiga &/or Xtandi, etc, increases the probability of defects. Perhaps ~20% of mCRPC cases harbor such defects [1].}

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/295...

[pjoshea13]

see also:

onclive.com/onclive-tv/dr-m...

-Patrick

[Hairlessness]

It's great to know such research is happening with PARP inhibitors. I'm six months in being treated impart with low dose interferon an inhibitor of cellular replication. It seems to be working, blocking or controlling the metastatic cancer and keeping the PSA down.

TY Dave

[Break60]

How does one go about getting tested?

[Hairlessness in reply to Break60]

You can request a DNA test with Guardant360 liquid biopsy through your oncologist. It's not cheap. If you're really interested you may need to consult with an oncologist that is using ammunotheraphy as an adjunct to the standard protocol. I had to change oncologist to receive treatment. Just a suggestion Dave

[Break60]

Patrick

So will this test tell you if certain treatments like 2nd line HT or whatever will not be effective so you don’t waste time trying them?

Bob

[pjoshea13 in reply to Break60]

Bob,

If you are referring to a test done before receiving any treatment, I don't believe so.

There has been interest in androgen receptor [AR] splice variants - particularly AR-V7 - since resistance to abiraterone due to AR-V7 prevalence is associated with a shorter time to enzalutamide resistance, & vice versa. Similarly, any change induced by one drug is likely to affect the performance of any other drug that also has the AR as the ultimate target.

It's unfortunate that the newer drugs select for cells that are much harder to manage. But that may expand the number of CRPC cases that are responsive to a PARP inhibitor.

-Patrick

[Break60]

Patrick

Yes I was wondering if research had gotten to the point where our genetic makeup could tell us in advance which drugs would be ineffective. I suppose we’re a long way from that but it will happen I’m sure.

Thanks

Bob