By Stephanie Murg, Managing Director, G2 Intelligence
A precision medicine approach is yielding valuable new insights into a common, aggressive form of prostate cancer. Researchers sequenced the DNA and RNA of tumor biopsy samples from 150 men with metastatic, castration-resistant prostate cancer (mCRPC), an advanced cancer that has stopped responding to standard hormone-based therapies, to conduct the first major analysis of this type of cancer in a clinical context. The study is published in the May 21 issue of Cell.
“One of the surprising findings in this study was that approximately 90 percent of cases harbored some kind of genetic anomaly that was clinically actionable, meaning we have potential treatments to target that specific aberration,” says co-senior author and principal investigator Arul Chinnaiyan, M.D., Ph.D., director of the Michigan Center for Translational Pathology and S.P. Hicks Professor of Pathology at the University of Michigan Health System (Ann Arbor, Mich.). “This suggests that clinical genomic sequencing could impact treatment decisions in a significant number of patients with disease.”
Among the cancer-driving genetic abnormalities identified, aberrations of the androgen receptor (AR), ETS (erythroblast transformation-specific) genes, TP53 (tumor protein p53), and PTEN (Phosphatase and tensin homolog) were frequent, appearing in 40 to 60 percent of cases, with TP53 and AR alterations enriched in mCRPC compared to primary prostate cancer. Fourteen percent of patients had a mutation in the BRCA1 or BRCA2 gene, which increase risk of breast and ovarian cancer. Additionally, 8 percent of cases were found to have an inherited genetic alteration, suggesting that genetic counseling may be appropriate for patients with prostate cancer.
Previous studies of mCRPC have been limited by difficulties in obtaining clinical samples from affected individuals as well as a lack of comprehensive genomic data for potentially actionable alterations, according to the authors. For this study, an international consortium of eight academic medical center clinical sites was established to capture fresh clinical samples as part of standard-of-care approaches or through a cohort of prospective clinical trials.
“This multi-institutional and international study demonstrates the feasibility of comprehensive and integrative genomics on prospective biopsies from individual patients to enable precision cancer medicine activities in this large patient population,” says Charles L. Sawyers, M.D., co-senior author and chair of the Human Oncology and Pathogenesis Program at Memorial Sloan Kettering Cancer Center (New York, N.Y.). “This study sets the stage for additional profiling efforts which may enable biological discovery and have immediate therapeutic relevance.”