Targeting FABP4/UCP2 axis to overcome cetuximab resistance in obesity-driven CRC with drug-tolerant persister cells.

ABSTRACT: Colorectal cancer (CRC) is closely linked to obesity, a condition that significantly impacts tumor progression and therapeutic resistance. Although cetuximab, an EGFR-targeting monoclonal antibody, is a cornerstone in metastatic CRC treatment, resistance often emerges, leading to poor outcomes. This study investigated the role of drug-tolerant persister (DTP) cells and their metabolic interactions within the tumor microenvironment (TME) in cetuximab resistance. Using patient-derived organoids and in vivo models, we identified the FABP4/UCP2 axis as a critical mediator of resistance. Organoids derived from cetuximab non-responders revealed upregulated FABP4 and UCP2 expression post-treatment. Coculture experiments with adipocytes showed that FABP4 and UCP2 promote lipid metabolic reprogramm

SUBMITTER: Cheng YC 

PROVIDER: S-EPMC11787020 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature