Biological, diagnostic and therapeutic relevance of the MET receptor signaling in head and neck cancer.

Nisa Hernandez, Lluis; Aebersold, Daniel; Giger, Roland; Zimmer, Yitzhak; Medova, Michaela (2014). Biological, diagnostic and therapeutic relevance of the MET receptor signaling in head and neck cancer. Pharmacology & therapeutics, 143(3), pp. 337-349. Elsevier 10.1016/j.pharmthera.2014.04.005

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Radiation Oncology
04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Ear, Nose and Throat Disorders (ENT)

UniBE Contributor:

Nisa Hernandez, Lluis; Aebersold, Daniel; Giger, Roland; Zimmer, Yitzhak and Medova, Michaela

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0163-7258

Publisher:

Elsevier

Language:

English

Submitter:

Beatrice Scheidegger

Date Deposited:

11 Mar 2015 15:28

Last Modified:

09 Nov 2015 10:03

Publisher DOI:

10.1016/j.pharmthera.2014.04.005

PubMed ID:

24786972

Uncontrolled Keywords:

Head and neck cancer, MET receptor tyrosine kinase, Prognostic impact, Targeted therapy, Treatment resistance

BORIS DOI:

10.7892/boris.61610

URI:

https://boris.unibe.ch/id/eprint/61610

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