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ABSTRACT
Introduction: Cyclin D-cyclin-dependent kinase (CDK) 4/6-inhibitor of CDK4/6-retinoblastoma (Rb) pathway hyperactivation is associated with hormone receptor-positive (HR+) breast cancer (BC). Ribociclib is an orally bioavailable, highly selective small molecule inhibitor of CDK4/6 that induces G1 arrest at sub-micromolar concentrations in a variety of pRb-positive cancer cells in vitro. Ribociclib is a new standard of care for metastatic HR+/HER2 negative metastatic breast cancer.
Area covered: In this article, we review the preclinical and clinical development of ribociclib as well as discussing the role for novel applications of these agents outside the arena of HR-positive, HER2-negative advanced breast cancer.
Expert opinion: Results of pivotal phase II and III trials investigating ribociclib in patients with advanced-stage (HR)-positive breast cancer have demonstrated a substantial improvement in progression-free survival, with a safe toxicity profile. Mechanisms of acquired resistance to CDK4/6 inhibitors are beginning to emerge and might enable rational post-CDK4/6 inhibitor therapeutic strategies to be identified. Extending the use of CDK4/6 inhibitors beyond ER-positive breast cancer is challenging, and will likely require biomarkers that are predictive of a response. The use of combination therapies to optimize CDK4/6 targeting is under development.
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.