BRCA2-Associated Prostate Cancer Primed to be Aggressive Before Treatment

A new study published in the journal, Nature Communications, has provided a potential explanation as to why men with an inheritable BRCA2 gene mutation tend to develop more aggressive forms of prostate cancer, which are difficult to treat. Previous research has shown that that up to 50 percent of patients with this type of prostate tumor die within five years of diagnosis.

In the current article, the researchers report that BRCA-associated prostate tumors are inherently aggressive in nature, even before treatment is started. They explain that the initial resistance to cancer therapy is a factor of the abnormalities in genes which regulate cell growth and proliferation in this type of prostate cancer.

The Canadian and Australian researchers studied 15 patients with BRCA2-inherited prostate cancer and compared them with 500 prostate cancer patients with a so-called ‘sporadic’ form of the disease. While the inherited form of prostate cancer affects fewer than 2 percent of men with the disease, the researchers say that their findings could help clinicians tailor treatment plans to individual patients.

“The pathways that we discovered to be abnormal in the localized BRCA2-associated cancers are usually only found in general population cancers when they become resistant to hormone therapy and spread through the body,” said Dr. Robert Bristow, clinician-scientist at Princess Margaret Cancer Centre, University Health Network in Toronto, Canada. “These include pathways related to the repair of DNA damage, cell division, the receptor for the male hormone testosterone and cell-to-cell signaling.

“We now know we need to explore the use of novel therapies to offset the BRCA2-associated aggressiveness earlier on in the treatment of these men and improve survival in an otherwise lethal tumor,” said Bristow. “This might include different types of chemotherapy or the use of molecular-targeted drugs that specifically target the changes associated with BRCA2 mutation.”

In another paper which was concurrently published by the researchers in the journal, Nature, Bristow and his colleagues identified a novel genetic fingerprint which could help doctors pinpoint when treatable prostate cancer turns more aggressive. This discovery was made after an analysis of 500 tumor samples collected from men with non-inherited prostate cancer.

“This is an exciting time in prostate cancer research in which the genetics of individual men and their cancers are beginning to dictate precise and customized treatment,” adds Bristow. “It is an example of the power of international collaboration and team science to crack the genetic code even in rarest of tumors.”