Our data show that PD0325901 sensitivity is increased in HPV (−) HNSCC harboring FAT1, CDKN2A, or NOTCH1 mutations, but decreased in tumors with other frequently mutated genes, including TP53, TTN, and CSMD3 (Fig. 1B), suggesting that these mutations may confer PD0325901 resistance through alternative mechanisms. This evidence concerns the gene CSMD3 and head and neck squamous cell carcinoma.