ArticleJCI insight2024
Targeting ketone body metabolism in mitigating gemcitabine resistance.
Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
6 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Urinary and cellular volatile organic compounds as biomarkers for urological cancers: a systematic review of GC-MS-based volatolomics.Metabolomics : Official journal of the Metabolomic Society · 2026Pooled it
- The significance of the ketolytic gene OXCT1 in metabolism, intracellular signaling and disease development.Cellular and molecular life sciences : CMLS · 2026Review
- The Function and Mechanism of OXCT1 in Tumor Progression as a Critical Ketone Body Metabolic Enzyme.Biomolecules · 2025Review
- Functional and Mechanistic Insights of 3-Hydroxybutyrate (3-OBA) in Bladder Cancer.Molecules (Basel, Switzerland) · 2025Article
- Circulating proteins and metabolites panel for noninvasive preoperative diagnosis of epithelial ovarian cancer.BMC medicine · 2025Article
- The role of neuroendocrine differentiation in treatment resistance of prostate cancer and intervention strategies.Frontiers in oncology · 2025Review
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Chemotherapy is often combined with surgery for muscle invasive and nonmuscle invasive bladder cancer (BCa). However, 70% of the patients recur within 5 years. Metabolic reprogramming is an emerging hallmark in cancer chemoresistance. Here, we report a gemcitabine resistance mechanism that promotes cancer reprogramming via the metabolic enzyme OXCT1. This mitochondrial enzyme, responsible for the rate-limiting step in β-hydroxybutyrate (βHB) catabolism, was elevated in muscle invasive disease and in patients with chemoresistant BCa. Resistant orthotopic tumors presented an OXCT1-dependent rise in mitochondrial oxygen consumption rate, ATP, and nucleotide biosynthesis. In resistant BCa, knocking out OXCT1 restored gemcitabine sensitivity, and administering the nonmetabolizable βHB enantiomer (S-βHB) only partially restored gemcitabine sensitivity. Suggesting an extrametabolic role for OXCT1, multi-omics analysis of gemcitabine sensitive and resistant cells revealed an OXCT1-dependent signature with the transcriptional repressor OVOL1 as a master regulator of epithelial differentiation. The elevation of OVOL1 target genes was associated with its cytoplasmic translocation and poor prognosis in a cohort of patients with BCa who have been treated with chemotherapy. The KO of OXCT1 restored OVOL1 transcriptional repressive activity by its nuclear translocation. Orthotopic mouse models of BCa supported OXCT1 as a mediator of gemcitabine sensitivity through ketone metabolism and regulating cancer stem cell differentiation.
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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.