CDK4/6 inhibitors in P16/HPV16-negative squamous cell carcinoma of the head and neck

Purpose: Addition of CDK4/6 inhibitors to a variety of established treatments in squamous cell carcinoma of the head and neck (SCCHN) has the potential to improve responses to other therapies and may help overcome treatment resistance. The SCCHN is a heterogeneous group of cancers of the oral cavity, the pharynx and the larynx with poor prognosis despite the aggressive multimodal therapies. In the past decade, significant advances were made in understanding of the molecular and genetic abnormalities leading to oncogenesis in SCCHN. Recent findings: Besides EGFR targeting agents, antiangiogenic agents have been shown to produce antitumor activity in these tumors. The cyclin D-cyclin-dependent kinase (CDK) 4/6-inhibitor of CDK4 (INK4)-retinoblastoma (Rb) pathway regulates cellular proliferation by controlling the G1 to S cell cycle checkpoint. In SCCHN, the Rb pathway is frequently altered through amplification of CCND1 (cyclin D1) or deletion of CDKN2A (cyclin-dependent kinase inhibitor 2A) coding for p16INK4A, and thus promoting proliferation. Summary: This article summarizes what we actually know of the place of CDK4/6 inhibitors in the therapeutic arsenal of SCCHN. CDK4/6 inhibitors could serve as a method to target these tumors, and both p16 loss and CCND1 amplification could be investigated as biomarkers.