BRAFV600E: implications for carcinogenesis and molecular therapy.
AffiliationDepartment of Histopathology, Trinity College, Sir Patrick Dun Research, Laboratory, Pathology Building, St. James' Hospital, Dublin 8, Ireland., email@example.com
Cell Transformation, Neoplastic/*genetics
Extracellular Signal-Regulated MAP Kinases/genetics/metabolism
Mitogen-Activated Protein Kinases/*genetics/metabolism
*Molecular Targeted Therapy
Proto-Oncogene Proteins B-raf/*genetics
MetadataShow full item record
CitationMol Cancer Ther. 2011 Mar;10(3):385-94.
JournalMolecular cancer therapeutics
AbstractThe 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.