Although the clinical application of monotherapy with CDK4/6 inhibitors might not be suitable for HNSCC, clinical trials in combination with cetuximab, radiotherapy, PI3K/mTOR inhibition or anti-PD-(L)1 antibodies are currently being conducted (NCT03065062, NCT03024489, NCT04000529) [206,207,208]. Here, PIK3CA is linked to head and neck squamous cell carcinoma.