Our genes are continually mutating as our cells go through their normal process of replicating themselves. However, our bodies are blessed with other genes whose job it is to identify these mutations and then repair them before they do any damage, like give us cancer.

Current research indicates that an estimated one-fifth or more of men with metastatic castration-resistant prostate cancer (mCRPC) have defects in these DNA repair genes (e.g., BRCA2, BRCA1, and others).

Early evidence suggests to us that these defects may be predictive of our having a positive therapeutic response to the class of drugs known as PARP inhibitors and also to platinum chemotherapy. Many clinical trials are examining this question, however, in most clinics, men with these defects are offered PARP inhibitors as a part of their treatment protocols.

Also, other studies are examining these genetic alterations as prognostic biomarkers for response to other currently available treatments. A smaller number of men (5%-10%) with mCRPC have evidence of microsatellite instability and defects in the DNA mismatch repair pathway, which may predict therapeutic response to immune checkpoint inhibitors.

Additionally, more than one-tenth of men with mCRPC carry genetic alterations of DNA repair in their germline DNA (the DNA we are born with), which may indicate high- to moderate-penetrance heritable cancer risk and also have important implications for family members.

Cascade genetic testing of a family can, in some cases, directly modified strategies for screening and prevention of multiple cancers. Further study in each of these areas is ongoing, although the potential for resounding effect is clear.

PMID: 29555412

DOI: 10.1016/j.urolonc.2018.02.014

Joel T. Nowak, MA, MSW wrote this Post.