Epacadostat Overcomes Cetuximab Resistance in Colorectal Cancer by Targeting IDO-Mediated Tryptophan Metabolism.

ABSTRACT: Primary or acquired mutations in RAS/RAF genes resulting in cetuximab resistance have limited its clinical application in colorectal cancer (CRC) patients. The mechanism of this resistance remains unclear. RNA sequencing from cetuximab-sensitive and -resistant specimens revealed an activation of the tryptophan pathway and elevation of IDO1 and IDO2 in cetuximab-resistant CRC patients. In vitro, in vivo, and clinical specimens confirmed the upregulation of IDO1and IDO2 and the Kyn/Trp after cetuximab treatment. Additionally, the IDO inhibitor, epacadostat, could effectively inhibit the migration and proliferation of cetuximab-resistant CRC cells while promoting apoptosis. Compared to epacadostat monotherapy, the combination of cetuximab and epacadostat showed a stronger synergistic anti-tum

SUBMITTER: Zhou Y 

PROVIDER: S-EPMC12127106 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature