Abstract
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.
Keywords
Abbreviations:
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)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: February 03, 2022
Accepted:
January 24,
2022
Received in revised form:
January 16,
2022
Received:
June 16,
2021
Identification
Copyright
© 2022 Elsevier Inc. All rights reserved.
