Researchers have identified a handful of mutations in patients with advanced prostate cancer for which therapeutics are already available, or in development. The genomes of 150 patients with metastatic (Stage 4) hormone-resistant disease were analyzed in order to develop a precision medicine framework for the treatment of advanced prostate cancer.
Indeed, 89% of the patients had “clinically actionable” mutations, meaning that therapies are already on the market (or in development) to treat the patients, although the approved indications for many products that target the mutations are not for prostate cancer, specifically.
Sixty-two percent of the patients with advanced hormone-resistant disease had mutations in the androgen receptor (as would be expected), however, 65% percent had mutations in other cancer-related genes including p53, PTEN, ETS transcription factors induced by the Ras/Raf mitogenic pathway. New genomic alterations in other oncogenes were also identified, including PIK3CA/B, R-spondin, BRAF/RAF1, APC, β-catenin, and ZBTB16/PLZF.
Importantly, the mutations in patients with advanced prostate cancer differed from those seen in patients with newly diagnosed disease. For example, aberrations of BRCA2, BRCA1, and ATM were observed at substantially higher frequencies (19.3% overall) compared to those in primary prostate cancers. BRCA mutations suggest that patients would benefit from PARP inhibitor therapy, which was recently approved for ovarian cancer. Study author Eliezer Van Allen remarked that the work “provides a strong argument that the genomics driving advanced prostate cancer is fundamentally different than primary prostate cancer.”
“The study’s findings echo a larger trend in cancer research: When it comes to identifying effective drug treatments, the site of the cancer is less significant than a particular cancer’s genetic blueprint.” This study provides additional validation of the concept that cancers of all types must be studied not according to their sites of origin, but rather according to the driver mutations that they possess. It also provides further evidence that our regulatory pathways for approval to use drugs and reimbursement for their use is flawed. Indeed, restricting approval and reimbursement to the approved claims (by cancer site of origin) does not allow for optimal, genomics-driven precision medicine.
Eight percent of the patients had these mutations in germ line cells, suggesting that screening of individuals with family histories of prostate cancer is appropriate.