Treatment sequence.

With so many systemic therapy options for metastatic castrate-resistant prostate cancer, it’s difficult to know what to use when. Sounds like a job for precision medicine. This review touches on where we’ve come and where we need to go next in determining predictive biomarkers for prostate cancer. It's worth noting the tools available for use now include assessing for the androgen receptor splice variant 7, which drastically diminishes the benefit of adding additional androgen signaling blockade (e.g., with enzalutamide or abiraterone), or for the loss of DNA repair genes: losses of mismatch repair or CDK12 are associated with sensitivity to immune checkpoint inhibition, while losses of homologous repair genes such as BRCA are associated with sensitivity to platinum-based chemo or PARP-inhibition. On the other hand, combined losses of tumor suppressor genes TP53 and RB1, common in small call histologies, typically signal that expanded androgen deprivation is a solid first go-to. TBL: Genome sequencing of castrate resistant mets makes therapeutic sense. | Ku, Nat Rev Urol 2019