An international collaboration of researchers is working to advance precision medicine for men suffering from prostate cancer.
The research team sequenced the DNA and RNA of tumor biopsies from 150 men with metastatic castration-resistant prostate cancer, which has stopped responding to standard hormone therapy, Memorial Sloan Kettering Cancer Center reported.
"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. This suggests that clinical genomic sequencing could impact treatment decisions in a significant number of patients with disease," says Arul Chinnaiyan, co-senior author and principal investigator of the study, director of the Michigan Center for Translational Pathology, and S.P. Hicks Professor of Pathology at the University of Michigan Health System.
Past studies that have taken a genetic look at localized prostate cancer have failed to find sufficient "actionable genetic alterations." This new research is the first to focus on this hard-to-treat subtype of prostate cancer.
"Up to now, precision cancer medicine activities in advanced prostate cancer have been limited by the lack of ability to acquire clinical samples from patients at the time of failure of hormone treatment and the lack of comprehensive genomic data for potentially actionable alterations," explains Dr. Charles L. Sawyers, co-senior author and chair of the Human Oncology and Pathogenesis Program at Memorial Sloan Kettering Cancer Center. "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. This study sets the stage for additional profiling efforts that may enable biological discovery and have immediate therapeutic relevance,"
The team found almost all of the tumors looked at in the study contained genetic features known to fuel cancer. The most common aberrations, seen in nearly two-thirds of the patients, were seen in the androgen receptor. This was expected because this disease has proven to no longer respond to androgen-blocking therapies.
Fourteen percent of the patients were found to have mutations in the BRCA1 or BRCA2 gene, which has been linked to breast and ovarian cancer in the past. Drugs known as PARP inhibitors have already been approved to treat BRCA-positive ovarian cancer, and could show promise for this type of prostate cancer as well. Eight percent of the patients possessed an inherited genetic alteration, which could mean genetic counseling is a viable addition to prostate cancer treatment for some patients.
In the future, the researchers plan to perform sequencing on biopsy samples from about 500 patients over the course of several years. They hope the large analysis will allow them to concretely link specific aberrations to treatment responses, allowing them to move forward in precision medicine for metastatic castration-resistant prostate cancer.
The findings were published in a recent edition of the journal Cell.
