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

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

Ngôn ngữ: eng

Ký hiệu phân loại: 627.12 Rivers and streams

Thông tin xuất bản: Germany : Cancer immunology, immunotherapy : CII , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 723970

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.
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