Patient-derived tumor xenograft study with CDK4/6 inhibitor plus AKT inhibitor for management of metastatic castrate resistant prostate cancer
In this study, we developed and characterized three metastatic prostate cancer PDTX models and developed 3D spheroids from the PDTX to compare their responses using a novel therapeutic combination. Guided by the genomic alterations in these models and interrelated mechanisms between androgen signaling axis, the cell cycle, and AKT pathway, we identified and investigated the combination of CDK4/6 inhibitors with AKT inhibitors as a potential therapy for patients with metastatic castration-resistant prostate cancer (mCRPC). Using 3-D spheroid drug assays followed by in vivo experiments in three unique PDTX models, these preclinical results highlight the potential use of CDK4/6 inhibitor with AKT inhibitors for the treatment of mCRPC in patients who have an intact retinoblastoma pathway, thereby providing experimental support and rationale for future clinical investigation.