ArticleMedical oncology (Northwood, London, England)2025
Derazantinib enhances gemcitabine efficacy in PDAC by attenuating the NF-κB and MAPK pathways to suppress MUC5AC expression.
Article in Medical oncology (Northwood, London, England), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
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. With RNA-seq, immunohistochemistry, Western blotting, and animal experiments, the effects of derazantinib on the malignant behaviors, signaling pathways in GEM-resistant PDAC cells and tumors were examined. Treatment with derazantinib and GEM synergistically inhibited the malignant behaviors of GEM-resistant PDAC cells and tumor growth by downregulating FGFR2 and FGFR3 expression. RNA-seq revealed upregulated MUC5AC expression in GEM-resistant PDAC, which was attenuated by derazantinib through inhibiting the MAPK and NF-κB signaling. Furthermore, higher levels of FGFR2 and FGFR3 expression were associated with worse survival of PDAC patients and negatively correlated with tumor differentiation. Moreover, the combination of derazantinib and GEM significantly inhibited the growth of GEM-resistant PDAC tumors in vivo. The data highlighted that higher levels of FGFR2, FGFR3, and MUC5AC expression promoted the progression and resistance to GEM in PDAC. Derazantinib treatment enhanced the sensitivity to GEM by attenuating the NF-κB and MAPK pathways to inhibit MUC5AC expression. Therefore, derazantinib may be a promising chemotherapeutic adjuvant for treating PDAC, particularly for patients with GEM resistance.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.