CDK4 and head and neck squamous cell carcinoma: In turn, this observation provided an opportunity to investigate the use of palbociclib, an FDA-approved cell cycle–targeted agent that can specifically inhibit CDK4/CDK6, to block cell-cycle signaling in combination with mTORi, and specifically in HPV− HNSCC cells, as HPV-positive cells are refractory to CDK inhibition due to the viral oncoprotein E7 causing Rb degradation (31).