Biological, diagnostic and therapeutic relevance of the MET receptor signaling in head and neck cancer.
Head and neck cancer constitutes the 6th most common malignancy worldwide and affects the crucial anatomical structures and physiological functions of the upper aerodigestive tract. Classical therapeutic strategies such as surgery and radiotherapy carry substantial toxicity and functional impairment. Moreover, the loco-regional control rates as well as overall survival still need to be improved in subgroups of patients. The scatter-factor/hepatocyte growth factor receptor tyrosine kinase MET is an established effector in the promotion, maintenance and progression of malignant transformation in a wide range of human malignancies, and has been gaining considerable interest in head and neck cancer over the last 15 years. Aberrant MET activation due to overexpression, mutations, tumor-stroma paracrine loops, and cooperative/redundant signaling has been shown to play prominent roles in epithelial-to-mesenchymal transition, angiogenesis, and responses to anti-cancer therapeutic modalities. Accumulating preclinical and translational evidence highly supports the increasing interest of MET as a biomarker for lymph node and distant metastases, as well as a potential marker of stratification for responses to ionizing radiation. The relevance of MET as a therapeutic molecular target in head and neck cancer described in preclinical studies remains largely under-evaluated in clinical trials, and therefore inconclusive. Also in the context of anti-cancer targeted therapy, a large body of preclinical data suggests a central role for MET in treatment resistance towards multiple therapeutic modalities in malignancies of the head and neck region. These findings, as well as the potential use of combination therapies including MET inhibitors in these tumors, need to be further explored.
Department of Radiation Oncology, Inselspital, Bern University Hospital, and University of Bern, 3010 Bern, Switzerland; Department of Clinical Research, University of Bern, 3010 Bern, Switzerland. Electronic address: lluis.nisa@dkf.unibe.ch.
Lluís
L
Nisa
Department of Radiation Oncology, Inselspital, Bern University Hospital, and University of Bern, 3010 Bern, Switzerland; Department of Clinical Research, University of Bern, 3010 Bern, Switzerland.
Daniel Matthias
DM
Aebersold
Department of Otorhinolaryngology-Head & Neck Surgery, Inselspital, Bern University Hospital, and University of Bern, 3010 Bern, Switzerland.
Roland
R
Giger
Department of Radiation Oncology, Inselspital, Bern University Hospital, and University of Bern, 3010 Bern, Switzerland; Department of Clinical Research, University of Bern, 3010 Bern, Switzerland.
Yitzhak
Y
Zimmer
Department of Radiation Oncology, Inselspital, Bern University Hospital, and University of Bern, 3010 Bern, Switzerland; Department of Clinical Research, University of Bern, 3010 Bern, Switzerland. Electronic address: michaela.medova@dkf.unibe.ch.
Michaela
M
Medová
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D006258:Head and Neck Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
Head and neck cancer; MET receptor tyrosine kinase; Prognostic impact; Targeted therapy; Treatment resistance