BRCA2-negative prostate cancer: new insights


New data from a research team at the Institute for Cancer Research in the UK suggest that — in men and women with a faulty BRCA2 gene — the development of breast cancer and prostate cancer follows a similar pathway.

The BRCA2 gene is involved in DNA repair and is known to have a role in the development of certain hereditary types of breast, ovarian, and prostate cancers.

Francis et al. have now been able to pinpoint cancer-causing DNA defects in male mice genetically engineered to lack BRCA2 in their prostate glands (so-called BRCA2 “knockout” mice). They then showed that prostate cells from the “knockout” mice accumulated DNA damage faster than it could be repaired. Over time, the disrupted DNA was expected to lead to damage in other, powerful anti-tumor genes, thus triggering the onset of cancer. The same process involving BRCA2 can lead to hereditary breast cancer in women.

The research reported by Francis and his colleagues builds on studies of a promising new class of drugs for BRCA2-linked breast cancers. These drugs are known as  poly-(ADP-ribose) polymerase inhibitors or more commonly PARP inhibitors. Such drugs offer the potential for development of more effective treatments for selected types of cancer, including some forms of breast and prostate cancer. Indeed, the most clinically advanced PARP inhibitor (BSI-201) is already in Phase III clinical trials for the treatment of so-called “triple-negative” breast cancer, and the CEO of Sanofi-Aventis, the company now developing this drug, has described some of the observed results as “stunning.”

Dr Lesley Walker, director of cancer information at Cancer Research UK, is quoted in a media release as having said: “We’ve made great progress in developing drugs for hereditary breast cancer — particularly in targeting cancers caused by specific faulty genes through drugs like PARP inhibitors. It would be fantastic if these drugs could ‘multi-task’ and treat prostate cancer too.”

We should conclude by noting that the incidence of BRCA2-related prostate cancer is very low by comparison with the overall incidence of prostate cancer in the USA each year. Even in the Ashkenazi Jewish community, where the incidence of BRCA1 and BRCA2 mutations is known to be relatively high compared to the US population as a whole, only about 5 percent of men diagnosed with prostate cancer were also shown to have one or other of these mutations. In the population as a whole, the incidence of BRCA2 mutations may be as low as 1 percent or perhaps even lower. In other words, only 1 man in100 diagnosed with prostate cancer (or less) is likely to have a form of prostate cancer triggered by the presence of a BRCA2-negative gene.

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