BRAFV600E: implications for carcinogenesis and molecular therapy.
Affiliation
Department of Histopathology, Trinity College, Sir Patrick Dun Research, Laboratory, Pathology Building, St. James' Hospital, Dublin 8, Ireland., cantweer@tcd.ieIssue Date
2012-02-01T10:44:54ZMeSH
AnimalsCell Transformation, Neoplastic/*genetics
Extracellular Signal-Regulated MAP Kinases/genetics/metabolism
Humans
Mice
Mitogen-Activated Protein Kinases/*genetics/metabolism
*Molecular Targeted Therapy
*Mutation
Proto-Oncogene Proteins B-raf/*genetics
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Mol Cancer Ther. 2011 Mar;10(3):385-94.Journal
Molecular cancer therapeuticsDOI
10.1158/1535-7163.MCT-10-0799PubMed ID
21388974Abstract
The mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway is frequently mutated in human cancer. This pathway consists of a small GTP protein of the RAS family that is activated in response to extracellular signaling to recruit a member of the RAF kinase family to the cell membrane. Active RAF signals through MAP/ERK kinase to activate ERK and its downstream effectors to regulate a wide range of biological activities including cell differentiation, proliferation, senescence, and survival. Mutations in the v-raf murine sarcoma viral oncogenes homolog B1 (BRAF) isoform of the RAF kinase or KRAS isoform of the RAS protein are found as activating mutations in approximately 30% of all human cancers. The BRAF pathway has become a target of interest for molecular therapy, with promising results emerging from clinical trials. Here, the role of the most common BRAF mutation BRAF(V600E) in human carcinogenesis is investigated through a review of the literature, with specific focus on its role in melanoma, colorectal, and thyroid cancers and its potential as a therapeutic target.Language
engISSN
1538-8514 (Electronic)1535-7163 (Linking)
ae974a485f413a2113503eed53cd6c53
10.1158/1535-7163.MCT-10-0799
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