It may soon be easier to link specific aberrations to response or resistance to specific treatments, making precision medicine more relevant and successful for metastatic castration resistant prostate cancer, according to a new international study published in the journal, Cell.1
Researchers from eight institutions in the United States and in Europe collaborated and sequenced the DNA and RNA of tumor biopsy samples from 150 men with metastatic castration resistant prostate cancer (mCRPC). Lead study investigator Arul Chinnaiyan, MD, PhD, of the University of Michigan, Ann Arbor, Mich., said this is the first major analysis of this common and aggressive type of cancer in a clinical context.2
Dr. Chinnaiyan said one of the surprising findings in this study was that approximately 90% of cases harbored some kind of genetic anomaly that was clinically actionable. He said the findings suggest that clinical genomic sequencing could impact treatment decisions in a significant number of patients with the disease.
Previous studies have looked at the genomic landscape of clinically localized prostate cancer and found few actionable genomic alterations. This is the first study to focus on this specific clinical subtype. Co-senior author Charles Sawyers, MD, said until 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 a lack of comprehensive genomic data for potentially actionable alterations.
Dr. Sawyer said this multi-institutional and international study demonstrated the feasibility of comprehensive and integrative genomics on prospective biopsies from individual patients to enable precision cancer medicine activities. He said this study sets the stage for additional profiling efforts which may enable biological discovery and have immediate therapeutic relevance.
The most common (nearly two-thirds of the patients) were aberrations in the androgen receptor and 14% of patients had a mutation in the BRCA1 or BRCA2 gene, which are already known to increase breast and ovarian cancer risk. PARP inhibitors have already been approved in BRCA-positive ovarian cancer, suggesting PARP inhibitors may be effective in some prostate cancers as well.
The researchers found that 8% of patients had an inherited genetic alteration. This suggests that genetic counseling may be appropriate for patients with prostate cancer. One of the unique aspects of this study is that it used fresh biopsy samples from living patients with mCRPC. Historically, it has been difficult to obtain a large enough quantity of quality tumor tissue, especially from bone biopsies, to make sequencing possible.
- Robinson D, Van Allen EM, Wu YM, et al. (2015). Integrative Clinical Genomics of Advanced Prostate Cancer. Cell, May 21; 161(5):1215-28.
- University of Michigan Comprehensive Cancer Center. (2015). Large international study finds 90% have anomaly that could influence treatment.