BRAF Mutation in Colorectal Cancers: From Prognostic Marker to Targetable Mutation
Open Access
- 3 November 2020
- Vol. 12 (11), 3236
- https://doi.org/10.3390/cancers12113236
Abstract
The Raf murine sarcoma viral oncogene homolog B (BRAF) mutation is detected in 8–12% of metastatic colorectal cancers (mCRCs) and is strongly correlated with poor prognosis. The recent success of the BEACON CRC study and the development of targeted therapy have led to the determination of BRAF-mutated mCRCs as an independent category. For nearly two decades, a growing body of evidence has established the significance of the BRAF mutation in the development of CRC. Herein, we overview both basic and clinical data relevant to BRAF-mutated CRC, mainly focusing on the development of treatment strategies. This review is organized into eight sections, including clinicopathological features, molecular features, prognosis, the predictive value of anti-epidermal growth factor receptor (EGFR) therapy, resistant mechanisms for BRAF-targeting treatment, the heterogeneity of the BRAF mutation, future perspectives, and conclusions. A characterization of the canonical mitogen-activated protein kinase (MAPK) pathway is essential for controlling this malignancy, and the optimal combination of multiple interventions for treatments remains a point of debate.Keywords
This publication has 203 references indexed in Scilit:
- Panitumumab and irinotecan versus irinotecan alone for patients with KRAS wild-type, fluorouracil-resistant advanced colorectal cancer (PICCOLO): a prospectively stratified randomised trialThe Lancet Oncology, 2013
- The Prognostic Role of BRAF Mutation in Metastatic Colorectal Cancer Receiving Anti-EGFR Monoclonal Antibodies: A Meta-AnalysisPLOS ONE, 2013
- Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysisThe Lancet Oncology, 2010
- Markers for EGFR pathway activation as predictor of outcome in metastatic colorectal cancer patients treated with or without cetuximabEuropean Journal of Cancer, 2010
- Kinase-Dead BRAF and Oncogenic RAS Cooperate to Drive Tumor Progression through CRAFCell, 2010
- Assessment of somatic k-RAS mutations as a mechanism associated with resistance to EGFR-targeted agents: a systematic review and meta-analysis of studies in advanced non-small-cell lung cancer and metastatic colorectal cancerThe Lancet Oncology, 2008
- Gene expression signature associated with BRAF mutations in human primary cutaneous melanomasMolecular Oncology, 2008
- RAF/RAS oncogenes and mismatch-repair statusNature, 2002
- Mutations of the BRAF gene in human cancerNature, 2002
- Gene expression profiling predicts clinical outcome of breast cancerNature, 2002