Selective CDK4/6 Inhibitors: Biologic Outcomes, Determinants of Sensitivity, Mechanisms of Resistance, Combinatorial Approaches, and Pharmacodynamic Biomarkers.

CDK4/6 inhibitors are now part of the standard armamentarium for hormone receptor-positive breast cancer. In this article, we review the biologic outcomes imposed by these drugs on cancer cells, determinants of response, mechanisms of intrinsic and acquired resistance, as well as combinatorial approaches emanating from mechanistic studies that may allow use of these agents to extend beyond breast cancer. In addition, we will address tumor-, imaging-, and blood-based pharmacodynamic biomarkers that can inform rationally designed trials as clinical development continues.