Derazantinib enhances gemcitabine efficacy in PDAC by attenuating the NF-κB and MAPK pathways to suppress MUC5AC expression.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is usually treated with gemcitabine (GEM)-based chemotherapy. However, resistance to GEM develops frequently. Aberrant fibroblast growth factor receptors (FGFR) signaling in PDAC is linked to advanced tumor stages and poor prognosis, making it a potential therapeutic target. This study aimed to explore whether inhibition of FGFR by derazantinib could reduce the resistance to GEM in PDAC. Human AsPC-1 and BxPC-3 PDAC cell lines were screened against a panel of FDA-approved compounds to identify the potential drug. Gem-resistant cell lines were subsequently utilized to validate the efficacy of derazantinib. The synergistic interaction between derazantinib and GEM was confirmed through combination-index analysis, clonogenic assays, and apoptosis assays.

SUBMITTER: Ye W 

PROVIDER: S-EPMC12753570 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature