ArticleSignal transduction and targeted therapy2025
Targeting AKR1B1 inhibits metabolic reprogramming to reverse systemic therapy resistance in hepatocellular carcinoma.
Article in Signal transduction and targeted therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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
18 citing papers in PubMed.
- Real-time NMR analysis of glutamine metabolism for screening anti-cancer agents in living cells.Magnetic resonance letters · 2027Article
- Integration of single-cell transcriptome of female early gonadal development in bovine, goats, and pigs.iScience · 2026Article
- Pan-cancer multi-omics analysis identifies SYNGR4 as a novel clinical prognostic biomarker and therapeutic target in lung adenocarcinoma.Discover oncology · 2026Article
- AKR1B1 promotes canine mammary tumorigenesis via activation of PI3K/AKT signaling and acts as a serum biomarker.Scientific reports · 2026Article
- NUPR1 as a central stress-adaptation node in cancer: integrating metabolic rewiring, cell death, and therapy resistance.Journal of biomedical science · 2026Review
- Targeting the OTU family: a core therapeutic strategy for reshaping the immunosuppressive microenvironment and reversing drug resistance in HCC by coordinating the autophagy-ferroptosis balance.Cell death discovery · 2026Review
- Targeting AKR1C1 overcomes lenvatinib resistance in hepatocellular carcinoma through the STAT3-ABC transporters pathway.Journal of gastrointestinal oncology · 2026Article
- A positive feedback loop between TKT and c-Myc drives TACE resistance in hepatocellular carcinoma.Cell death discovery · 2026Article
- A bibliometric analysis of research trends and emerging frontiers in heat shock proteins and hepatocellular carcinoma from 2015 to 2025.Discover oncology · 2026Article
- Multi-omics SMR and experimental supportive analyses decipher causal drivers hepatocellular carcinoma.BMC cancer · 2026Article
- Targeting AKR1B1 reprograms tumor-associated macrophages to enhance antitumor immunity.Journal for immunotherapy of cancer · 2026Article
- DRESIS 2.0: the comprehensive landscape of drug resistance information.Nucleic acids research · 2026Article
- Spatiotemporal control of mitoribosome-mediated metabolic reprogramming in cancer: implications for heterogeneity and therapeutic targeting.Frontiers in cell and developmental biology · 2026Review
- Article
- Dynamic Evolution of the Tumor Immune Microenvironment in Malignant Tumors and Emerging Therapeutic Paradigms.MedComm · 2025Review
- Aldose Reductase Involvement in EMT: Emerging Insights and Current Proposed Molecular Mechanisms.Biology · 2025Review
- Adrenomedullin orchestrates treatment resistance in hepatocellular carcinoma via immune microenvironment remodeling.Frontiers in genetics · 2025Article
- Chronic Psychological Stress in Oncogenesis: Multisystem Crosstalk and Multimodal Interventions.Research (Washington, D.C.) · 2025Review
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, and resistance to systemic therapies remains a significant clinical challenge. This study investigated the mechanisms by which metabolic reprogramming contributes to systemic treatment resistance in HCC. We established HCC cell lines with multidrug resistance characteristics and observed enhanced metabolic activity in these cells. Integrated multiomics analyses revealed hyperactive glucose‒lipid and glutathione metabolic pathways that play critical roles in supporting tumor cell proliferation and survival. We constructed a metabolic reprogramming atlas for HCC-resistant cells and identified aldo-keto reductase (Aldo-keto reductase family 1 Member B1, AKR1B1) as a key regulator of this reprogramming, which sustains drug resistance by regulating energy metabolism and enhancing stress tolerance. Importantly, AKR1B1 expression levels are closely associated with drug resistance and poor prognosis in HCC patients. The secretory nature of AKR1B1 not only underscores its predictive value but also facilitates the intercellular transmission of drug resistance. In terms of overcoming resistance, the AKR1B1 inhibitor epalrestat significantly mitigated drug resistance when it was used in combination with standard therapies. These findings underscore the importance of metabolic reprogramming in the development of HCC resistance. AKR1B1, a key enzyme that regulates metabolic reprogramming, has been identified as a potential biomarker and therapeutic target, providing new insights into overcoming resistance in HCC treatment.
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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 Socratic graph.