Researchers Identify New Treatment Target in BRCA2-Mutant Prostate Cancer

Germline BRCA2 mutations are associated with poorer outcome in prostate cancer and now researchers think they know why.

Germline BRCA2 mutations are associated with poorer outcome in prostate cancer and now researchers think they know why. In addition, the researchers have identified one particular genetic abnormality that is common in the tumors of BRCA2-mutation carriers. They hope that these new findings can lead to a new type of targeted therapy for men with prostate cancer who are BRCA2- mutation carriers.

“Men with BRCA2 mutations tend to have more aggressive prostate cancers than those who don’t, and our new study finds a potential reason in the genetic abnormalities within these tumors,” said study investigator Professor Rosalind Eeles, FMedSci MA FCRP FRCR PhD, who is a Professor of Oncogenetics at The Institute of Cancer Research, London, England.1

Professor  Eeles and colleagues analyzed whether there was a signature set of copy number alterations (CNA) that could aid to the identification of BRCA2-mutated tumors. The researchers believe that if they can identify a specific genetic signature it may be possible to better understand the aggressive clinical behavior associated with BRCA2- mutated tumors.

The study, published in the Annals of Oncology,2 was a collaboration between scientists at The Institute of Cancer Research in London and scientists at the Spanish National Cancer Research Centre in Madrid. The investigators profiled DNA from prostate cancer and healthy tissue in 20 men who carried BRCA2 germline mutations and 40 men who did not. The subjects in this study were enrolled in the UK Genetics Prostate Cancer Study (UKGPCS), EMBRACE (Epidemiological Study of Familial Breast Cancer), and the IMPACT study.

The investigators found that the men with BRCA2 mutations were more likely to have extra copies of a gene called c-MYC, which potentially was leading to uncontrolled cell growth. They concluded that targeting c-MYC may therefore be a potential treatment for patients with the BRCA2 mutation.

“Detailing the genetic mutations within the tumors of BRCA2-mutation carriers allows us to start identifying new treatment targets, and devising new personalized treatment strategies. We believe a first step could be to target c-MYC, since we’ve provided evidence that this is often present in increased copy numbers in BRCA-mutant cancers,” said Professor Eeles.

Previously published studies have demonstrated that prostate cancer in BRCA2 mutation carriers tends to be may be associated with aggressive disease, a higher Gleason score, and a higher prostate-specific antigen (PSA) level at the time of diagnosis. In addition, men who harbor this mutation have been found to have a higher tumor stage and/or grade at the time of diagnosis.

It is hoped that these new findings may lead to new agents that may improve survival in men with prostate cancer who harbor the BRCA2 mutation. Previous studies have shown that the median survival for men with a BRCA2 mutation is approximately 4 years compared to 8 years in men with a BRCA1 mutation.