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<p>BRAF-mutated colorectal cancer correlates with poor prognosis and limited response to standard treatments. Combining immune checkpoint inhibitors with BRAF/MEK inhibitors shows promise against BRAF-mutant melanoma in both preclinical and clinical trials. Therefore, we hypothesized that the treatment would be effective against BRAF-mutant colorectal cancer. In this study, we assessed the efficacy of combining immune checkpoint inhibitors with BRAF and/or MEK inhibitors in BRAF-mutant colorectal cancers. We treated BRAF V600E colorectal cancer cells HT-29 and SNU-1235 with encorafenib (BRAF inhibitor) and binimetinib (MEK inhibitor) and assessed the degrees of MAPK inhibition, JAK/STAT inhibition, cell viability, apoptosis, and the expression of antigen presenting machinery. We also inoculated HT-29 cells into mice and treated them with an immune checkpoint inhibitor (durvalumab), encorafenib, and binimetinib for 4&#xa0;weeks. We found that treatment with BRAF inhibitor, MEK inhibitor, or their combination led to significant tumor growth reduction, along with the MAPK and JAK/STAT pathway inhibition, antigen presenting machinery induction, and cytotoxic T cell activation. Our study demonstrates the potential effectiveness of combining immune checkpoint inhibitors with BRAF or MEK inhibitors for BRAF-mutated colorectal cancers.</p>

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Antitumor effects of immunotherapy combined with BRAF and MEK inhibitors in BRAF V600E metastatic colorectal cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月19日

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  • Eunyoung Tak,
  • Hye-In An,
  • Amy Sinyoung Lee,
  • Kyuyoung Han,
  • Jiwan Choi,
  • Hyung-don Kim,
  • Yong Sang Hong,
  • Sun Young Kim,
  • Eun Kyung Choi,
  • Jeong Eun Kim,
  • Tae Won Kim

摘要

BRAF-mutated colorectal cancer correlates with poor prognosis and limited response to standard treatments. Combining immune checkpoint inhibitors with BRAF/MEK inhibitors shows promise against BRAF-mutant melanoma in both preclinical and clinical trials. Therefore, we hypothesized that the treatment would be effective against BRAF-mutant colorectal cancer. In this study, we assessed the efficacy of combining immune checkpoint inhibitors with BRAF and/or MEK inhibitors in BRAF-mutant colorectal cancers. We treated BRAF V600E colorectal cancer cells HT-29 and SNU-1235 with encorafenib (BRAF inhibitor) and binimetinib (MEK inhibitor) and assessed the degrees of MAPK inhibition, JAK/STAT inhibition, cell viability, apoptosis, and the expression of antigen presenting machinery. We also inoculated HT-29 cells into mice and treated them with an immune checkpoint inhibitor (durvalumab), encorafenib, and binimetinib for 4 weeks. We found that treatment with BRAF inhibitor, MEK inhibitor, or their combination led to significant tumor growth reduction, along with the MAPK and JAK/STAT pathway inhibition, antigen presenting machinery induction, and cytotoxic T cell activation. Our study demonstrates the potential effectiveness of combining immune checkpoint inhibitors with BRAF or MEK inhibitors for BRAF-mutated colorectal cancers.