title: HGF/Met Signaling in Head and Neck Cancer: Impact on the Tumor Microenvironment.
abstract: Studies to date have revealed several major molecular alterations that contribute to head and neck squamous cell carcinoma (HNSCC) initiation, progression, metastatic spread, and therapeutic failure. The EGFR is the only FDA-approved therapeutic target, yet responses to cetuximab have been limited. Activation and cross-talk of cellular receptors and consequent activation of different signaling pathways contribute to limited activity of blockade of a single pathway. The hepatocyte growth factor (HGF) receptor, Met, has been implicated in HNSCC tumorigenesis and EGFR inhibitor resistance. HGF, the sole ligand of Met, is overexpressed in the tumor microenvironment. The role of HGF/Met signaling in proliferation, metastasis, and angiogenesis has been investigated in HNSCC, leading to clinical trials with various Met inhibitors and HGF antibodies. However, the role of the HGF/Met signaling axis in mediating the tumor microenvironment has been relatively understudied in HNSCC. In this review, we discuss the functional roles of Met and HGF in HNSCC with a focus on the tumor microenvironment and the immune system. Clin Cancer Res; 22(16); 4005-13. ©2016 AACR.
authors.affiliation: Department of Otolaryngology, University of California San Francisco, San Francisco, California. Department of Oral and Maxillofacial Plastic Surgery, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hartmann
authors.affiliation: Department of Otolaryngology, University of California San Francisco, San Francisco, California.
authors.forename: Neil E
authors.initials: NE
authors.lastname: Bhola
authors.affiliation: Department of Otolaryngology, University of California San Francisco, San Francisco, California. jennifer.grandis@ucsf.edu.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Grandis
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D058990:Molecular Targeted Therapy; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D000077195:Squamous Cell Carcinoma of Head and Neck; D016896:Treatment Outcome; D059016:Tumor Microenvironment
chemical_list: D000970:Antineoplastic Agents; D017228:Hepatocyte Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met