The emerging role of MET/HGF inhibitors in oncology.

Abstract:

:The N-methyl-N'-nitroso-guanidine human osteosarcoma transforming gene (MET) receptor tyrosine kinase and its ligand hepatocyte growth factor (HGF) control cellular signaling cascades that direct cell growth, proliferation, survival, and motility. Aberrant MET/HGF activation has been observed in many tumor types, can occur by multiple mechanisms, and promotes cellular proliferation and metastasis via growth factor receptors and other oncogenic receptor pathways. Thus, MET/HGF inhibition has emerged as targeted anticancer therapies. Preclinically, neoplastic and metastatic phenotypes of several tumor cells, including non-small cell lung cancer, hepatocellular carcinoma, and gastric cancer, were abrogated by MET inhibition. Ongoing clinical development with tivantinib, cabozantinib, onartuzumab, crizotinib, rilotumumab, and ficlatuzumab has shown encouraging results. These trials have established a key role for MET in a variety of tumor types. Evidence is emerging for identification of aberrant MET activity biomarkers and selection of patient subpopulations that may benefit from targeted MET and HGF inhibitor treatment.

journal_name

Cancer Treat Rev

journal_title

Cancer treatment reviews

authors

Scagliotti GV,Novello S,von Pawel J

doi

10.1016/j.ctrv.2013.02.001

subject

Has Abstract

pub_date

2013-11-01 00:00:00

pages

793-801

issue

7

eissn

0305-7372

issn

1532-1967

pii

S0305-7372(13)00032-7

journal_volume

39

pub_type

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