Reversion mutation - re-challenging with a PARP no longer an option

[HopingForTheBest1]

After being on Olaparib PARP for 2 years, I recently had a Guardant liquid biopsy. It identified that my BRCA2 mutation has become a "reversion" mutation, which means that PARPs will no longer be an effective treatment for me. A reversion mutation restores the ability of the gene to produce a functional protein.

[Har036]

I’m sorry to hear that for you. I was hopeful that you could restart it. My husband has been on Lynparza for the past 25 months and his PSA has been undetectable. He also had 6 Xofigo treatments last year. I believe that the combination of the two treatments was the key. Today is his lab appointment and we’re praying that all is well. You are also in our prayers. I hope that you’ll find the next responsive treatment soon.

[HopingForTheBest1 in reply to Har036]

I am currently on chemo combo of Jevtana & Carboplatin. Having my 11th treatment today. Latest blood work shows PSA down from 48 to 26 since #10 3 weeks prior.

[MateoBeach]

perhaps that might be a favorable reversion???

BRAC1/2 mutations disable the encoded proteins from functioning correctly to facilitate repair of DNA (mismatch repair MMR) through the two repair processes of homologous repair HR, or non-homologous end joining NHEJ. And if the damaged DNA cannot be repaired, then triggering the death of the cell, apoptosis.

So while it is great to have these drugs for those whose cancer is caused or progresses due to the mutations in these genes. Is it not better to have non-mutated or reversion to properly functioning mechanisms?

I have not been clear on this question. Paul

en.m.wikipedia.org/wiki/BRCA1

[MateoBeach in reply to MateoBeach]

BTW, that is a lot of chemo my friend. Hoping you are tolerating it well.

[HopingForTheBest1 in reply to MateoBeach]

Yes, tolerating well. Although, liver enzymes ALT & AST are high and red blood cells are low.

[Grandpa4]

I think there is increasing data these drugs work in some patients without known mutation in DNA repair. If it worked for you in the past seems worth a try.

[HopingForTheBest1]

Unfortunately, re-challenging with a PARP is out of the question and will not be effective due to the reversion mutation. I did get 3 separate concurring opinions from different well known cancer centers.