Rationale for Using Irreversible Epidermal Growth Factor Receptor Inhibitors in Combination with Phosphatidylinositol 3-Kinase Inhibitors for Advanced Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is a common and debilitating form of cancer characterized by poor patient outcomes and low survival rates. In HNSCC, genetic aberrations in phosphatidylinositol 3-kinase (PI3K) and epidermal growth factor receptor (EGFR) pathway genes are common, and small molecules targeting these pathways have shown modest effects as monotherapies in patients. Whereas emerging preclinical data support the combined use of PI3K and EGFR inhibitors in HNSCC, in-human studies have displayed limited clinical success so far.