On the Rise of Cyclin-Dependent Kinase Inhibitors in Breast Cancer: Progress & Ongoing Challenges.

Abstract

Given marked improvements in progression free and overall survival in the metastatic setting, along with a favorable toxicity profile, the cyclin-dependent kinase 4/6 inhibitors (CDK4/6i’s) have become standard of care in frontline therapy for hormone receptor positive metastatic breast cancer (HR+ MBC). Despite initial durable responses, however, virtually all patients with MBC will eventually progress; as such, rigorous studies into the mechanisms of resistance are ongoing, as is an effort to develop rational sequencing strategies and identify subgroups that will retain benefit upon progression. Herein we briefly discuss the grounds for initial experimentation on the CDK pathway and the early successes to which it gave rise. We then focus on what we know about key resistance mechanisms and discuss correlative biomarker studies as a vital strategy for advancing the field of targeted therapy in MBC.