HGF/Met Signaling in Head and Neck Cancer: Impact on the Tumor Microenvironment

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....

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Bibliographic Details
Published in:Clinical cancer research 2016-08, Vol.22 (16), p.4005-4013
Main Authors: Hartmann, Stefan, Bhola, Neil E, Grandis, Jennifer R
Format: Article
Language:English
Subjects:
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Carcinoma, Squamous Cell - drug therapy
Carcinoma, Squamous Cell - etiology
Carcinoma, Squamous Cell - metabolism
Carcinoma, Squamous Cell - pathology
Clinical Trials as Topic
Drug Evaluation, Preclinical
Head and Neck Neoplasms - drug therapy
Head and Neck Neoplasms - etiology
Head and Neck Neoplasms - metabolism
Head and Neck Neoplasms - pathology
Hepatocyte Growth Factor - metabolism
Humans
Molecular Targeted Therapy
Prognosis
Proto-Oncogene Proteins c-met - metabolism
Signal Transduction - drug effects
Squamous Cell Carcinoma of Head and Neck
Treatment Outcome
Tumor Microenvironment
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Summary: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.
ISSN:1078-0432
1557-3265
DOI:10.1158/1078-0432.CCR-16-0951