Personalized Medicine for Advanced Prostate Cancer: Encouraging Results

Anthony L. Komaroff, MD reviewing Robinson D et al. Cell 2015 May 21.

Identifying an individual's genetic mutations could help prioritize treatment options.

“Personalized medicine” is defined as studying an individual's genome to help with selection of proper therapies. A multicenter U.S. team systematically collected metastatic tumor tissue (from lymph nodes, bone, liver, and other sources) from 150 patients with castration-resistant prostate cancer and compared this tissue's genetic makeup with that of tumor tissue from 440 primary prostate cancers. They determined the nucleic acid sequences of all exons (gene sequences that encode proteins) and of all genes that were being transcribed into messenger RNA. The goal was to identify sequence variants seen in metastatic tumors but not in the primary tumors — variations that might explain metastasis and resistance to androgen-deprivation treatments.

The team discovered a large group of sequence differences in the metastases, most often involving the gene for the androgen receptor and the TP53 gene. Some of the sequence aberrations involved genes known to be important in other malignancies, including BRAF, BRCA2, and BRCA1. The investigators determined that 89% of the patients had “clinically actionable aberrations” — changes in genes that already are targets of approved drugs or of drugs in late development stages.

Citation(s):

Robinson D et al. Integrative clinical genomics of advanced prostate cancer. Cell 2015 May 21; 161:1215.