Mutations in two genes well known for increasing the risk of breast and ovarian cancer may also play an important role in advanced prostate cancer, researchers said, an unexpected discovery that could lead to new treatments for some men with the disease.
Analysis of DNA from tumor tissue obtained from 150 men with late-stage prostate cancer revealed mutations in the BRCA1 or BRCA2 genes in about 15% of cases, according to a study published Thursday by the journal Cell. An additional 5% of the men had aberrations in genes with similar function.
Previous studies had turned up such mutations in a small fraction of men with early-stage disease, but “we had no idea they were that common” in advanced prostate cancer, said Charles Sawyers, chair of the Human Oncology and Pathogenesis Program at Memorial Sloan Kettering Cancer Center and one of the leaders of the study.
The finding suggests that some 20% of men who have stopped responding to conventional hormone therapy may be candidates for an emerging class of drugs called PARP-inhibitors, researchers said. One such drug, olaparib from AstraZeneca PLC, was approved by regulators in December for advanced ovarian cancer in women with BRCA mutations. Cisplatin-based chemotherapy could be another option for such men.
“Prior to this no one would have entertained treating these patients with those drugs,” Dr. Sawyers said. Clinical trials would be required to confirm their effectiveness and role in the disease, he added.
The study’s broader finding concluded that 89% of the patients had culprit genetic anomalies that could be vulnerable to either drugs already on the market or experimental compounds now being tested by drug companies—also a result researchers termed “remarkable.”
Overall, the study suggests “that patients with advanced prostate cancer should get some level of molecular profiling done” to potentially widen and improve their treatment options, said Arul Chinnaiyan, director of the University of Michigan’s Center for Translational Pathology, who helped lead the study.