Co-targeting SRC overcomes resistance to BRAF inhibitors in colorectal cancer.

ABSTRACT:

Background

BRAF^V600E mutations occur in ∼10% of colorectal cancer (CRC) patients, leading to poor prognosis. Although BRAF-targeted therapy is ineffective in CRC, adding EGFR inhibitors (EGFRi) improves efficacy, yet patient survival remains suboptimal. This study explores SRC as a key mediator of resistance to BRAF inhibitors (BRAFi) in preclinical BRAF^V600E CRC models, and its potential as a therapeutic target.

Methods

We studied SRC using BRAF-mutated and wild-type CRC cell lines with CRISPR/Cas9 knockouts and lentiviral overexpression. We tested SRC, BRAF, EGFR, and JNK targeting drugs, assessing protein expression, cell viability, proliferation, migration, apoptosis, and cell cycle. CRC cell line-derived xenograft (CDX) and patient-derived xenograf

SUBMITTER: Rubio-Cuesta B 

PROVIDER: S-EPMC12322152 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature