Study data published Thursday in the journal Cell clarify the genetic backgrounds of men with metastatic, castration-resistant prostate cancer, revealing that the majority of cases are sensitive to drugs already available or under development. Study author Johann de Bono commented "this is a game changer," adding "it's really going to alter the way we deal with this lethal disease."
Study researchers sequenced tumours from 150 patients with metastatic, castration-resistant prostate cancer that had spread to the bones, soft tissues, lymph nodes and livers. Results showed that 89 percent of men with the disease carried "clinically actionable" mutations, including 62.7 percent with aberrations in the androgen receptor and 65 percent in other cancer-related genes.
The scientists determined that 19.3 percent of the men had mutations in ATM, BRCA1 and BRCA2. Faults in the latter two genes are linked to sensitivity to PARP inhibitors, which were originally developed to treat breast and ovarian cancers, but are now being tested in prostate cancer. Mutations were also uncovered in the PI3K and RAF gene families. Further, the work revealed that 8 percent of the men were born with genetic faults that predisposed them to prostate cancer, strengthening the case for screening people with a family history of the disease.
"This map will guide our future treatment and trials for this group of different lethal diseases," said de Bono, adding "we're describing this study as prostate cancer's Rosetta stone - because of the ability it gives us to decode the complexity of the disease, and to translate the results into personalised treatment plans for patients."
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." As a next phase of the research, the investigators said they plan to sequence cells from at least 500 patients with metastatic, castration-resistant prostate cancer and follow the course of their disease to assess how they respond to personalised treatment.