Combination AURKA and WEE1 inhibition exhibits efficacy in EGFR or pan-ERBB inhibitor resistant head and neck squamous cell carcinoma

Many HNSCCs overexpress the ERBB family member EGFR, and EGFR inhibitors (EGFRis) and pan-ERBB inhibitors (ERBBis) are clinically active in treatment of locally advanced, metastatic or recurrent HNSCC. However, resistance to these inhibitors typically develops, often associated with epithelial-mesenchymal transition (EMT).

Aurora kinase A (AURKA), a mitotic regulator with expanded signaling functions in tumors, has been reported to reverse EGFR resistance in EGFR-mutated lung cancer. To identify strategies to overcome resistance in HNSCC, we developed HNSCC cell models that were treatment-naïve parental, or selected for resistance to the EGFRi erlotinib, or the ERBBi afatinib. The resistant HNSCC models had typically undergone partial EMT, consistent with clinical resistance, associated with upregulation of the AURKA partner protein NEDD9.