期刊
CANCER TREATMENT REVIEWS
卷 60, 期 -, 页码 1-11出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.ctrv.2017.08.002
关键词
Lung cancer; Targeted therapy; MET oncogene; MET exon 14 variant
类别
资金
- Italian Association for Cancer Research [AIRC-MFAG 14282]
- International Association for Lung Cancer (IASLC)
The discovery of druggable oncogenic drivers (i.e. EGFR and ALK), along with the introduction of comprehensive tumor genotyping techniques into the daily clinical practice define non-small-cell lung cancer (NSCLC) as a group of heterogeneous diseases, requiring a context-personalized clinico-therapeutical approach. Among the most investigated biomarkers, the MET proto-oncogene has been extensively demonstrated to play a crucial role throughout the lung oncogenesis, unbalancing the proliferation/apop-tosis signaling and influencing the epithelial-mesenchymal transition and the invasive phenotype. Nevertheless, although different mechanisms eliciting the aberrant MET-associated oncogenic stimulus have been detected in lung cancer (such as gene amplification, increased gene copy number, mutations and MET/HGF overexpression), to date no clinically impactful results have been achieved with anti-MET tyrosine kinase inhibitors and monoclonal antibodies in the context of an unselected or MET enriched population. Recently, MET exon 14 splicing abnormalities have been identified as a potential oncogenic target in lung cancer, able to drive the activity of MET inhibitors in molecularly selected patients. In this paper, the major advancement and drawbacks of MET history in lung cancer are reviewed, underlying the renewed scientific euphoria related to the recent identification of MET exon 14 splicing variants as an actionable oncogenic target. (c) 2017 Elsevier Ltd. All rights reserved.
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