ArticleInternational journal of molecular sciences2019
Hexokinase-II Inhibition Synergistically Augments the Anti-tumor Efficacy of Sorafenib in Hepatocellular Carcinoma.
Article in International journal of molecular sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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
28 citing papers in PubMed, 42 citations in OpenAlex.
- Review
- Navigating the Labyrinth of Hepatocellular Carcinoma: Leveraging AI/ML for Precision Oncology.Oncology research · 2026Review
- The role and therapeutic potential of glucose metabolism in multidrug resistance of cancer.Frontiers in cell and developmental biology · 2025Review
- Metabolic reprogramming in hepatocellular carcinoma: mechanisms of immune evasion and therapeutic implications.Frontiers in immunology · 2025Review
- Review
- Role of lactate and lactate metabolism in liver diseases (Review).International journal of molecular medicine · 2024Review
- [Liver cancer treatment with mitochondrial homeostasis].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2024Article
- The PI3K/Akt Pathway and Glucose Metabolism: A Dangerous Liaison in Cancer.International journal of biological sciences · 2024Review
- The Promoting Role of HK II in Tumor Development and the Research Progress of Its Inhibitors.Molecules (Basel, Switzerland) · 2023Review
- The Role of Reprogrammed Glucose Metabolism in Cancer.Metabolites · 2023Review
- Sodium butyrate inhibits aerobic glycolysis of hepatocellular carcinoma cells via the c-myc/hexokinase 2 pathway.Journal of cellular and molecular medicine · 2022Article
- Fasting improves therapeutic response in hepatocellular carcinoma through p53-dependent metabolic synergism.Science advances · 2022Article
- Correlation of Glucose Metabolism with Cancer and Intervention with Traditional Chinese Medicine.Evidence-based complementary and alternative medicine : eCAM · 2022Review
- Role of hypoxia in the tumor microenvironment and targeted therapy.Frontiers in oncology · 2022Review
- Research progress of abnormal lactate metabolism and lactate modification in immunotherapy of hepatocellular carcinoma.Frontiers in oncology · 2022Review
- Sulfarotene, a synthetic retinoid, overcomes stemness and sorafenib resistance of hepatocellular carcinoma via suppressing SOS2-RAS pathway.Journal of experimental & clinical cancer research : CR · 2021Article
- Review
- Hexokinase 2 in Cancer: A Prima Donna Playing Multiple Characters.International journal of molecular sciences · 2021Review
- Metabolic Classification and Intervention Opportunities for Tumor Energy Dysfunction.Metabolites · 2021Review
- A hexokinase isoenzyme switch in human liver cancer cells promotes lipogenesis and enhances innate immunity.Communications biology · 2021Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
This study aimed to examine whether inhibition of hexokinase (HK)-II activity enhances the efficacy of sorafenib in in-vivo models of hepatocellular carcinoma (HCC), and to evaluate the prognostic implication of HK-II expression in patients with HCC. We used 3-bromopyruvate (3-BP), a HK-II inhibitor to target HK-II. The human HCC cell line was tested as both subcutaneous and orthotopic tumor xenograft models in BALB/c nu/nu mice. The prognostic role of HK-II was evaluated in data from HCC patients in The Cancer Genome Atlas (TCGA) database and validated in patients treated with sorafenib. Quantitative real-time PCR, western blot analysis, and immunohistochemical staining revealed that HK-II expression is upregulated in the presence of sorafenib. Further analysis of the endoplasmic reticulum-stress network model in two different murine HCC models showed that the introduction of additional stress by 3-BP treatment synergistically increased the in vivo/vitro efficacy of sorafenib. We found that HCC patients with increased HK-II expression in the TCGA database showed poor overall survival, and also confirmed similar results for TCGA database HCC patients who had undergone sorafenib treatment. These results suggest that HK-II is a promising therapeutic target to enhance the efficacy of sorafenib and that HK-II expression might be a prognostic factor in HCC.
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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.