HDAC and MEK inhibition synergistically suppresses HOXC6 and enhances PD-1 blockade efficacy in BRAF^V600E-mutant microsatellite stable colorectal cancer.

ABSTRACT:

Background

B-Raf proto-oncogene, serine/threonine kinase (BRAF)^V600E-mutant microsatellite stable (MSS) colorectal cancer (CRC) constitutes a distinct CRC subgroup, traditionally perceived as minimally responsive to standard therapies. Recent clinical attempts, such as BRAF inhibitors (BRAFi) monotherapy and combining BRAFi with other inhibitors, have yielded unsatisfactory efficacy. This study aims to identify a novel therapeutic strategy for this challenging subgroup.

Methods

We first performed a large-scale drug screening using patient-derived organoid models and cell lines to pinpoint potential therapies. Subsequently, we investigated the synergistic effects of identified effective inhibitors and probed their cooperative mechanisms. Concurrently, we explored t

SUBMITTER: Sun Z 

PROVIDER: S-EPMC11749543 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature