c-Met Signaling as a Therapeutic Target in Head and Neck Cancer

Despite a dearth of activating driver mutations in head and neck squamous cell carcinoma (HNSCC), aberrant activation of the oncogenes, epidermal growth factor receptor (EGFR), and c-Met is near-universal in human papillomavirus (HPV)-negative disease. Although EGFR activation drove the successful development of the anti-EGFR monoclonal antibody cetuximab in HNSCC, no c-Met-targeting therapy has gained regulatory approval. Inhibition of the c-Met pathway may subvert oncogenesis within the tumor-intrinsic compartment, blocking tumoral proliferation, invasion, migration, and metastasis, or the tumor-extrinsic compartment, modulating the immunosuppressive tumor microenvironment. This review discusses the rationale and current drug development strategies for targeting c-Met or its exclusive ligand hepatocyte growth factor (HGF) in HNSCC.