CDK4 and head and neck squamous cell carcinoma: Similarly, the PI3K/mTOR pathway was found to be overactivated in palbociclib-resistant breast cancer cells, with increased levels of CCND1 and CDK4 translation that could be reverted by PI3K/mTOR inhibition (49), and palbociclib-based high-throughput combination drug screens showed a significant synergistic effect when palbociclib was combined with PI3K, EGFR, or MEK inhibitors in HNSCC (50).