2. Academic Validation
  3. Antitumor effects of immunotherapy combined with BRAF and MEK inhibitors in BRAF V600E metastatic colorectal cancer

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

  • Cancer Immunol Immunother. 2025 Mar 19;74(5):154. doi: 10.1007/s00262-025-04005-3.
Eunyoung Tak # 1,  Hye-In An # 2,  Amy Sinyoung Lee 2,  Kyuyoung Han 2,  Jiwan Choi 2,  Hyung-Don Kim 3,  Yong Sang Hong 3,  Sun Young Kim 3,  Eun Kyung Choi 4,  Jeong Eun Kim 5,  Tae Won Kim 3 6
Affiliations

Affiliations

  • 1 Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
  • 2 Department of Convergence Medicine, Asan Medical Institute of Convergence Science and Technology (AMIST), Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
  • 3 Department of Oncology, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Republic of Korea.
  • 4 Department of Radiation Oncology, Asan Preclinical Evaluation Center for Cancer TherapeutiX, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
  • 5 Department of Oncology, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Republic of Korea. jeongeunkim@amc.seoul.kr.
  • 6 Asan Preclinical Evaluation Center for Cancer TherapeutiX, Asan Medical Center, Seoul, 05505, Republic of Korea.
  • # Contributed equally.
PMID: 40105971 DOI: 10.1007/s00262-025-04005-3
Abstract

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.

Keywords

Anti-PD-L1; BRAF V600E; BRAF inhibitor; Immunotherapy; MEK inhibitor.

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