Colorectal Cancer with BRAF V600E Mutation: Trends in Immune Checkpoint Inhibitor Treatment

Colorectal cancer (CRC) with BRAF V600E mutation presents a formidable scientific and clinical challenge due to its aggressive nature and poor response to standard therapeutic approaches. BRAF V600E mutation-induced conspicuous activation of the MAPK pathway contributes to the relentless tumor progr...

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Bibliographic Details
Published in:Critical reviews in oncology/hematology 2024-09, p.104497, Article 104497
Main Authors: Liu, Mengling, Liu, Qing, Hu, Keshu, Dong, Yu, Sun, Xun, Zou, Zhiguo, Ji, Dingkun, Liu, Tianshu, Yu, Yiyi
Format: Article
Language:English
Subjects:
BRAF V600E mutation
colorectal cancer
immune checkpoint inhibitors
MAPK inhibition
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Summary:Colorectal cancer (CRC) with BRAF V600E mutation presents a formidable scientific and clinical challenge due to its aggressive nature and poor response to standard therapeutic approaches. BRAF V600E mutation-induced conspicuous activation of the MAPK pathway contributes to the relentless tumor progression. Nevertheless, the efficacy of multi-targeted MAPK pathway inhibition remains suboptimal in clinical practice. Patients with high microsatellite instability (MSI-H) have shown favorable results with immune checkpoint inhibitors (ICIs). The combination of the MAPK pathway inhibition with ICIs has recently emerged as a promising regimen to improve clinical outcomes in the microsatellite stable (MSS) subgroup of BRAF V600E-mutant metastatic CRC patients. In this review, we elucidate the unique tumor biology of BRAF V600E-mutant CRC, with a particular focus on the immune features underlying the rationale for ICI treatments in the MSI-H and MSS subpopulations, then highlight the trends in clinical trials of the ICI therapy for BRAF V600E-mutant metastatic CRC. •BRAF V600E mutation-mediated hyperactivation of MAPK signaling creates a unique biology in CRC.•BRAF V600E mutation has no significant impact on the T-cell-mediated anti-tumor immune responses in CRC.•Inhibiting the MAPK pathway reshapes the immune microenvironment in BRAF V600E-mutant mCRC.•ICIs are effective for BRAF V600E-mutant MSI-H mCRC.•ICI and MAPK inhibition is a promising combination for BRAF V600E-mutant MSS mCRC.
ISSN:1040-8428
1879-0461
1879-0461
DOI:10.1016/j.critrevonc.2024.104497