LAUSR

Approximately One-third of metastatic castration-resistant prostate cancer (mCRPC) patients exhibited primary abiraterone resistance. To identify alternative treatment for abiraterone non-responders, we performed drug discovery analyses using the L1000 database using differentially expressed genes identified in tumor biopsies and patient-derived xenograft (PDX) tumors between abiraterone responders and non-responders enrolled in PROMOTE trial. This approach identified 3 drugs, including TOP2 inhibitor mitoxantrone, CDK4/6 inhibitor palbociclib, and pan-CDK inhibitor PHA-793887. These drugs significantly suppressed the growth of abiraterone-resistant cell lines and PDX models. Moreover, we identified 11 genes targeted by all three drugs that were associated with worse outcomes in both the PROMOTE and Stand Up To Cancer cohorts. This 11 gene panel might also function as biomarkers to select the 3 alternative therapies for this subgroup of CRPC patients, warranting further clinical investigation.