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Review
. 2009 Feb;63(2):169-79.
doi: 10.1016/j.lungcan.2008.06.011. Epub 2008 Jul 30.

MET as a target for treatment of chest tumors

Nicole A Cipriani  1 , Oyewale O Abidoye, Everett Vokes, Ravi Salgia
Affiliations
Review

MET as a target for treatment of chest tumors

Nicole A Cipriani et al. Lung Cancer. 2009 Feb.

Abstract

The receptor tyrosine kinase MET has been studied of a large variety of human cancers, including lung and mesothelioma. The MET receptor and its ligand HGF (hepatocyte growth factor) play important roles in cell growth, survival and migration, and dysregulation of the HGF-MET pathway leads to oncogenic changes including tumor proliferation, angiogenesis and metastasis. In small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), and malignant pleural mesothelioma (MPM), MET is dysregulated via overexpression, constitutive activation, gene amplification, ligand-dependent activation, mutation or epigenetic mechanisms. New drugs targeted against MET and HGF are currently being investigated in vitro and in vivo, with promising results. These drugs function at a variety of steps within the HGF-MET pathway, including MET expression at the RNA or protein level, the ligand-receptor interaction, and tyrosine kinase function. This paper will review the structure, function, mechanisms of tumorigenesis, and potential for therapeutic inhibition of the MET receptor in lung cancer and mesothelioma.

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Figures

Figure 1
Figure 1. MET Structure
SEMA (Semaphorin-like); PSI (found in Plexins, Semaphorins, and Integrins); IPT (found in lg-like regions, Plexins and Transcription factors); TM (Trans-Membrane); JM (Juxta-Membrane); TK (Intracellular Tyrosine Kinase); S (Serine); Y (Tyrosine); NSCLC (non-small cell lung carcinoma); SCLC (small cell lung carcinoma); MPM (malignant pleural mesothelioma).
Figure 2
Figure 2. The MET Pathway
PYK2 (protein tyrosine kinase 2); PXN (paxillin); FAK (focal adhesion kinase); SOS (son of sevenless); GRB2 (growth factor receptor-bound protein 2); GAB1 (GRB2-associated binding protein 1); RHO (Ras homolog gene family); RAC1 (ras-related C3 botulinum toxin substrate 1); CDC42 (cell division cycle 42); Pl3K (phosphoinositol 3 kinase).
Figure 3
Figure 3. MET regulation
Figure 4
Figure 4. Anti-MET Therapeutics
RNA (ribonucleic acid); siRNA (small interference RNA); shRNA (short hairpin RNA); miRNA (micro RNA); DNA (deoxyribonucleic acid); HSP (heat shock protein); HGF (hepatocyte growth factor); Ab (antibody); RTK (receptor tyrosine kinase); P (phosphate).
See this image and copyright information in PMC

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