期刊
CANCER TREATMENT REVIEWS
卷 53, 期 -, 页码 61-69出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.ctrv.2016.12.001
关键词
MEK; Resistance; NSCLC; CRC
类别
资金
- Associazione Italiana per la Ricerca sul Cancro (AIRC) [14800, 17778]
The mitogen-activated protein kinases (MAPKs) mediate intracellular signals activated by a wide variety of extracellular stimuli. The activation of the RAS-RAF-MEK-MAPK cascade culminates in the regulation of gene transcription promoting cancer cell proliferation, survival, migration and angiogenesis. MEK (mitogen-activated protein kinase kinase-MAPKK) 1/2 is a transducer of the growth factor receptor-RAS-RAF-MAPK signalling cascade and plays a relevant role in development and progression of human cancers, such as colorectal cancer (CRC), non small cell lung cancer (NSCLC). Direct inhibition of MEK is a promising strategy and several inhibitors are currently under evaluation in clinical trials showing initial clinical activity in different tumours. MEK activation, by different genetic mechanisms, has been described for both intrinsic and acquired resistance to drugs targeting the EGFR (Epidermal Growth Factor Receptor)-RAS-RAF pathway in CRC, NSCLC. Combination therapies with chemotherapy and/or with molecular targeted agents are warranted and biomarkers studies are needed to identify those tumours dependent on MEK signalling. (C) 2016 Elsevier Ltd. All rights reserved.
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