It may soon be easier to treat metastatic castration-resistant prostate cancer (mCRPC) based on genetic anomalies. A new international study suggested it may be possible to link specific aberrations to response or resistance to specific treatments in 90% of cases.

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 mCRPC. They found that patients with mCRPC harbor genomic alterations in PIK3CA/B, RSPO, RAF, APC, B-catenin, and ZBTB16 and 23% harbor DNA repair pathway aberrations.1

“We were surprised that upwards of 90% of patients with advanced prostate cancer have clinically actionable aberrations. Not including androgen receptor (AR) as a target, over 60% of patients have actionable aberrations in other pathways. This suggests that precision medicine approaches may be especially important in patients with metastatic disease,” said principal study investigator Arul Chinnaiyan, MD, PhD, professor of pathology at the University of Michigan Health System in Ann Arbor, MI.

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He said the results from this study showed that clinical genomic sequencing could impact treatment decisions in a significant number of patients with metastatic disease.

Previous studies have examined the genomic landscape of clinically localized prostate cancer and found few actionable genomic alterations.

However, that does not appear to be the case with this specific clinical subtype. The study demonstrated that AR, ETS genes, and TP53 and PTEN alterations were present in 40% to 60% of cases.

In addition, AR and TP53 alterations were enriched in cases of metastatic disease compared to primary prostate cancer.

“I was surprised that we could successfully generate cancer genome data from most patients. There was a lot of skepticism in advance because these biopsies, particularly of bone lesions, are not straightforward,” study investigator Charles Sawyers, MD, told Cancer Therapy Advisor.

Dr. Sawyers, who is the chair of the Human Oncology and Pathogenesis Program at Memorial Sloan-Kettering Cancer Center in New York, NY, said until now precision medicine activities in advanced prostate cancer have been limited for several reasons.

He said there has been a lack of ability to acquire clinical samples from patients at the time of failure of hormone treatment. In addition, Dr. Sawyers said there has been a lack of comprehensive genomic data for potentially actionable alterations.

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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.