Treatment of Advanced BRAF-Mutated Colorectal Cancer: Where We Are and Where We Are Going

Published:February 03, 2022DOI:


      In recent years, studies on the molecular typing of colorectal cancer have matured, and the V-raf murine sarcoma viral oncogene homolog B (BRAF) of the mitogen-activated protein kinase pathway has been shown to be an important effector molecule of this pathway and regulates the occurrence and development of colorectal cancer. Clinical observations indicate that colorectal cancer patients harboring the BRAF V600E mutation have a worse prognosis than BRAF wild type patients. Several resistance mechanisms have been identified that have led to the development of different treatment strategies, which have shown encouraging activity in early clinical trials. Therefore, a reasonable combination of targeted therapies is expected to further enhance the efficacy of selective BRAF inhibitors. Moreover, some CRC patients with high microsatellite instability or a mismatch repair deficiency seem to be susceptible to checkpoint inhibitors with objective and sustained clinical responses, providing new opportunities for patients with advanced disease. This article primarily explores 3 aspects of the treatment strategies for advanced BRAF-mutated colorectal cancer; chemotherapy, targeted therapy, and immunotherapy.



      BRAF (V-raf murine sarcoma viral oncogene homolog B), CRC (colorectal cancer), CR (conserved regions), ERK (extracellular regulated protein kinases), RPTKs (receptor tyrosine kinases), PDGF (platelet-derived growth factor), Grb2 (growth factor receptor binding protein 2), SOS (son of sevenless), GDP (Guanosine diphosphate), GTP (guanosine triphosphate), MAPK (mitogen-activated protein kinase), PI3K (phosphatidylinositol-3-linase), PKA (protein kinase A), EPAC (exchange protein directly activated by cAMP by cAMP), BIM (Bcl-2-like protein 11), WT (wildtype), PFS (progression-free survival), OS (overall survival), P-PS (post-progression-free survival), EGFR (epidermal growth factor receptor), NCCN (national comprehensive cancer network), VEGF (vascular endothelial growth factor), Beva (Bevacizumab), FOLFOXIRI (fluorouracil + calcium folinate + oxaliplatin + irinotecan), FAD (food and drug administration), CR (complete response), PR (partial response), ASCO (American society of clinical oncology), SD (stable disease), PTEN (phosphatase and tensin homologs), PIK3CA (phosphatidylinositol-3-kinase catalyzed α polypeptide), PD-1/PD-L1 (programmed death-1/ligand-1 programmed death), CTLA-4 (anti-gen-4 associated with cytotoxic T lymphocytes), MSI-H (high microsatellite instability), dMMR (mismatch repair deficient), CIMP (CpG island methylator phenotype), MLH1 (MutL homolog 1), pMMR (mismatch repair proficient), MSS (microsatellite stable), TMB (tumor mutational burden)
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