What are the Important DNA Repair Mutations in Prostate Cancer?

There has been much discussion as well as clinical trials about the use of personal genetic information, specifically the presence of mutations in the DNA repair genes such as BRACA2, with the successful use of PARP-Inhibitors and in confirming our understanding that the occurrences of these genetic mutations are an indication of a poor prognosis.  

The discussion in the prostate cancer community has specifically surrounded the BRACA gene, but what are the other DNA repair genes that seem to have a similar effect on both prognosis and the efficacy of the newly developing PARP Inhibitor drugs?  

You should know the other, currently identified DNA repair gene mutations that have been identified to date, they are mutations of: 



In a recently discussed abstract presented at ESMO 2018, the TRITON2 study evaluating the efficacy of a PARP-Inhibitor in men with one of these DNA alterations, in an unplanned interim analysis, 85 men have been enrolled (enrollment is not completed). Of these 85 men, 45 have a BRCA1/2 alteration, 18 have an ATM alteration, 13 have a CDK12 alteration, and 9 have other mutations in the HRR pathway. 

Amongst the group of men with the DNA repair gene mutations, 88% (14/16) men had a response to olaparib (a PARP-Inhibitor), compared with 6% (2/33) of men who were biomarker negative (did not have one of these mutations). 

There are many phase II and phase III studies currently ongoing investigating the role of single agent and combination therapies with PARP inhibitors.

Joel T Nowak, MA, MSW