Journal ArticleDOI
Drug development of MET inhibitors : targeting oncogene addiction and expedience
TLDR
Recent progress in the development of molecules that inhibit MET function are discussed and their application in a subset of human tumours that are potentially responsive to MET-targeted therapies is considered.Abstract:
The MET tyrosine kinase stimulates cell scattering, invasion, protection from apoptosis and angiogenesis, thereby acting as a powerful expedient for cancer dissemination. MET can also be genetically selected for the long-term maintenance of the primary transformed phenotype, and some tumours appear to be dependent on (or 'addicted' to) sustained MET activity for their growth and survival. Because of its dual role as an adjuvant, pro-metastatic gene for some tumour types and as a necessary oncogene for others, MET is a versatile candidate for targeted therapeutic intervention. Here we discuss recent progress in the development of molecules that inhibit MET function and consider their application in a subset of human tumours that are potentially responsive to MET-targeted therapies.read more
Citations
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Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach?
TL;DR: It is argued that modulating the unique redox regulatory mechanisms of cancer cells might be an effective strategy to eliminate these cells.
Journal ArticleDOI
MET signalling: principles and functions in development, organ regeneration and cancer.
TL;DR: The MET tyrosine kinase receptor promotes tissue remodelling, which underlies developmental morphogenesis, wound repair, organ homeostasis and cancer metastasis, by integrating growth, survival and migration cues in response to environmental stimuli or cell-autonomous perturbations.
Journal ArticleDOI
Rational, biologically based treatment of EGFR -mutant non-small-cell lung cancer
William Pao,Juliann Chmielecki +1 more
TL;DR: This Review summarizes recent developments aimed at treating and ultimately curing Epidermal growth factor receptor-mutant lung cancer.
Journal ArticleDOI
Molecular targeted therapies in hepatocellular carcinoma.
TL;DR: To overcome the complexity of genomic aberrations in HCC, combination therapies will be critical and a molecular classification of HCC based on genome‐wide investigations and identification of patient subclasses according to drug responsiveness will lead to a more personalized medicine.
Journal ArticleDOI
Pathogenesis, Diagnosis, and Management of Cholangiocarcinoma
Sumera Rizvi,Gregory J. Gores +1 more
TL;DR: A better understanding of the imaging characteristics of iCCAs is gained and advanced cytologic techniques to detect pCCAs are developed, along with advances in classification, diagnosis, and treatment.
References
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Journal ArticleDOI
MET Amplification Leads to Gefitinib Resistance in Lung Cancer by Activating ERBB3 Signaling
Jeffrey A. Engelman,Kreshnik Zejnullahu,Tetsuya Mitsudomi,Youngchul Song,Courtney Hyland,Joon Oh Park,Neal I. Lindeman,Christopher-Michael Gale,Xiaojun Zhao,James J. Christensen,Takayuki Kosaka,Alison J. Holmes,Andrew M. Rogers,Federico Cappuzzo,Tony Mok,Charles Lee,Bruce E. Johnson,Lewis C. Cantley,Pasi A. Jänne +18 more
TL;DR: It is proposed that MET amplification may promote drug resistance in other ERBB-driven cancers as well after it was found that amplification of MET causes gefitinib resistance by driving ERBB3 (HER3)–dependent activation of PI3K, a pathway thought to be specific to EGFR/ERBB family receptors.
Journal ArticleDOI
Epidermal growth factor receptor mutations in lung cancer
TL;DR: 'oncogenic shock' is described as a mechanistic explanation for the apoptosis that follows the acute treatment of susceptible cells with kinase inhibitors, essential to the successful use of targeted therapies in common epithelial cancers.
Journal ArticleDOI
Met, metastasis, motility and more
TL;DR: Pivotal roles for Met in development and cancer have been established: Met controls cell migration and growth in embryogenesis; it also controls growth, invasion and metastasis in cancer cells; and activating Met mutations predispose to human cancer.
Journal Article
Liver regeneration : Frontiers in medicine: Regeneration
TL;DR: This review attempts to integrate the findings of the last three decades and looks toward clues as to the nature of the causes that trigger this fascinating organ and cellular response.
Journal ArticleDOI
Stromal fibroblasts in cancer initiation and progression
TL;DR: It is revealed that fibroblasts have a more profound influence on the development and progression of carcinomas than was previously appreciated and this has important therapeutic implications.
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