Large Genomic Analysis Reveals New Genetic Anomalies in Advanced Prostate Cancer Patients

Large Genomic Analysis Reveals New Genetic Anomalies in Advanced Prostate Cancer Patients

A study recently published in the journal Cell revealed genetic anomalies in biopsy samples from patients with advanced prostate cancer through a large multi-institutional integrative clinical sequencing approach. The study is entitled “Integrative Clinical Genomics of Advanced Prostate Cancer” and was developed by an international collaboration of researchers.

Prostate cancer is the second most common cancer in men with almost one million new cases diagnosed each year worldwide. It is a curable cancer that can range from slow-growing tumors to rapidly progressing aggressive tumors, which are more difficult to treat.

Previous studies have focused on the genomic characterization of clinically localized prostate cancer, but have only found a few genomic alterations. This collaborative research team has now sequenced the DNA and RNA of cancer biopsy samples from 150 men with metastatic castration-resistant prostate cancer, an advanced cancer form that is no longer responsive to standard hormone-based therapies. This study represents the first major analysis of this aggressive cancer in a clinical context.

The research team found that almost all the tumor samples analyzed had a genetic anomaly known to promote cancer development. The most common anomaly found, present in almost two-thirds of the patients, was in the androgen receptor. This observation was not surprising, since castration-resistant prostate cancers are non-responsive to conventional androgen-blocking therapies. Mutations in the BRCA1 or BRCA2 genes, known to be linked to a higher risk of breast and ovarian cancer, were found in 14% of the patients. In addition, 8% of the patients analyzed had an inherited genetic alteration and 23% anomalies in DNA repair pathways.

“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,” said in a news release one of the study’s co-senior authors Dr. Arul Chinnaiyan from the University of Michigan Health System, and co-leader of the Stand Up to Cancer-Prostate Cancer Foundation Dream Team.

“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 which may enable biological discovery and have immediate therapeutic relevance,” concluded the study’s co-senior author Dr. Charles L. Sawyers from the Memorial Sloan-Kettering Cancer Center and co-leader of the Stand Up to Cancer-Prostate Cancer Foundation Dream Team.

The team plans to sequence and monitor a total of at least 500 patients with advanced prostate cancer. As androgen receptor mutations and other genetic anomalies are being detected in a large proportion of patients, the team hopes to be able to connect specific anomalies to the patient’s response or resistance to specific treatments, making precision medicine more relevant and successful in cases of metastatic castration-resistant prostate cancer.