Toward a Molecular Classification of Colorectal Cancer: The Role of BRAF
Open Access
- 1 January 2013
- journal article
- review article
- Published by Frontiers Media SA in Frontiers in Oncology
- Vol. 3, 281
- https://doi.org/10.3389/fonc.2013.00281
Abstract
Different genetic aberrations of BRAF have been reported in various malignancies. BRAF is member of the RAS/RAF/MEK/ERK pathway and constitutive activity of this pathway can lead to increased cellular growth, invasion, and metastasis. The most common activating BRAF mutation in colorectal cancer is the V600E mutation, which is present in 5-15% of all tumors, and up to 80% of tumors with high microsatellite instability harbor this mutation. BRAF mutation is associated with proximal location, higher age, female gender, MSI-H, high grade, and mucinous histology, and is a marker of poor prognosis in colorectal cancer. The role of BRAF mutation as a predictive marker in respect of EGFR targeted treatments is controversial. BRAF V600 selective inhibitors have been approved for the treatment of V600 mutation positive metastatic melanoma, but the response rates in colorectal cancer are poor. This might be due to innate resistance mechanisms of colorectal cancers against the treatment solely targeting BRAF. To overcome resistance the combination of treatments, simultaneous inhibition of BRAF and MEK or PI3K/mTOR, might emerge as a successful therapeutic concept.Keywords
This publication has 72 references indexed in Scilit:
- Validation of Next Generation Sequencing Technologies in Comparison to Current Diagnostic Gold Standards for BRAF, EGFR and KRAS Mutational AnalysisPLOS ONE, 2013
- Clinicopathological relevance of BRAF mutations in human cancerPathology, 2013
- Mutations and Deregulation of Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Cascades Which Alter Therapy Response.Oncotarget, 2012
- Targeting Mutant BRAF in MelanomaThe Cancer Journal, 2012
- Assessment of BRAF V600E mutation status by immunohistochemistry with a mutation-specific monoclonal antibodyActa Neuropathologica, 2011
- Targeting BRAF for patients with melanomaBritish Journal of Cancer, 2010
- RAF protein-serine/threonine kinases: Structure and regulationBiochemical and Biophysical Research Communications, 2010
- RAF gene fusions are specific to pilocytic astrocytoma in a broad paediatric brain tumour cohortActa Neuropathologica, 2010
- Targets of Raf in tumorigenesisCarcinogenesis: Integrative Cancer Research, 2010
- Oncogenic RAF1 rearrangement and a novel BRAF mutation as alternatives to KIAA1549:BRAF fusion in activating the MAPK pathway in pilocytic astrocytomaOncogene, 2009