Cabozantinib, a Promising Therapeutic Strategy for Resistant Head and Neck Squamous Cell Carcinoma Patients

Local or metastatic relapses following surgery, radiotherapy and chemotherapy (cisplatin) are the leading causes of death of patients with head and neck squamous cell carcinoma (HNSCC). In the current study, we showed that acquired resistance to radiotherapy and cisplatin of HNSCC cells and patients depends on overexpression of c-MET and AXL. Cabozantinib, a VEGFR, c-MET and AXL inhibitor, decreased migration, invasion and proliferation, and induced mitotic catastrophe and apoptotic cell death of naive and radiotherapy- and cisplatin-resistant HNSCC cells.Cabozantinib inhibited the growth of experimental HNSCC in mice by inhibiting tumor cell proliferation and angiogenesis. Cabozantinib inhibited the growth and the metastatic spread of experimental HNSCC in zebrafish. The efficacy of cabozantinib on experimental models of HNSCC was further confirmed on viable sections of surgically removed specimens of human HNSCC. These results suggest that cabozantinib is highly relevant for the treatment of HNSCC patients following relapses on radiotherapy and cisplatin.