PDX of esophageal squamous cell carcinoma with CDKN2A/2B loss was more sensitive to CDK4/6 inhibitors than those with wild-type CDKN2A/2B.371 Palbociclib has shown a promising effect in HNSCC, and the adverse effect of palbociclib is well tolerated. Here, CDKN2A is linked to esophageal squamous cell carcinoma.