Targeting the hepatocyte growth factor-cMET axis in cancer therapy

George R. Blumenschein, Gordon Mills, Ana M. Gonzalez-Angulo

Research output: Contribution to journalReview article

183 Citations (Scopus)

Abstract

The hepatocyte growth factor (HGF) and its receptor, the transmembrane tyrosine kinase cMET, promote cell proliferation, survival, motility, and invasion as well as morphogenic changes that stimulate tissue repair and regeneration in normal cells but can be co-opted during tumor growth. MET overexpression, with or without gene amplification, has been reported in a variety of human cancers, including breast, lung, and GI malignancies. Furthermore, high levels of HGF and/or cMET correlate with poor prognosis in several tumor types, including breast, ovarian, cervical, gastric, head and neck, and non-small-cell lung cancers. Gene amplification and protein overexpression of cMET drive resistance to epidermal growth factor receptor family inhibitors, both in preclinical models and in patients. It is increasingly apparent that the HGF-cMET axis signaling network is complex, and rational combinatorial therapy is needed for optimal clinical efficacy. Better understanding of HGF-cMET axis signaling and the mechanism of action of HGF-cMET inhibitors, along with the identification of biomarkers of response and resistance, will lead to more effective targeting of this pathway for cancer therapy.

Original languageEnglish (US)
Pages (from-to)3287-3296
Number of pages10
JournalJournal of Clinical Oncology
Volume30
Issue number26
DOIs
StatePublished - Sep 10 2012
Externally publishedYes

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Hepatocyte Growth Factor
Gene Amplification
Neoplasms
Proto-Oncogene Proteins c-met
Breast Neoplasms
Therapeutics
Epidermal Growth Factor Receptor
Non-Small Cell Lung Carcinoma
Protein-Tyrosine Kinases
Regeneration
Cell Survival
Stomach
Neck
Biomarkers
Head
Cell Proliferation
Lung
Growth
Proteins

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Targeting the hepatocyte growth factor-cMET axis in cancer therapy. / Blumenschein, George R.; Mills, Gordon; Gonzalez-Angulo, Ana M.

In: Journal of Clinical Oncology, Vol. 30, No. 26, 10.09.2012, p. 3287-3296.

Research output: Contribution to journalReview article

Blumenschein, George R. ; Mills, Gordon ; Gonzalez-Angulo, Ana M. / Targeting the hepatocyte growth factor-cMET axis in cancer therapy. In: Journal of Clinical Oncology. 2012 ; Vol. 30, No. 26. pp. 3287-3296.
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