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Lactate, histone lactylation and cancer hallmarks

Published online by Cambridge University Press:  09 January 2023

Xinyu Lv ,
Yingying Lv  and
Xiaofeng Dai Open the ORCID record for Xiaofeng Dai [Opens in a new window]
Xinyu Lv
Affiliation:
Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China
Yingying Lv
Affiliation:
Department of Clinical Laboratory, Shanghai Pudong New Area People's Hospital, Shanghai 201299, China
Xiaofeng Dai*
Affiliation:
Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China
*
Author for correspondence: Xiaofeng Dai, E-mail: xiaofeng.dai@jiangnan.edu.cn
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Abstract

Histone lactylation, an indicator of lactate level and glycolysis, has intrinsic connections with cell metabolism that represents a novel epigenetic code affecting the fate of cells including carcinogenesis. Through delineating the relationship between histone lactylation and cancer hallmarks, we propose histone lactylation as a novel epigenetic code priming cells toward the malignant state, and advocate the importance of identifying novel therapeutic strategies or dual-targeting modalities against lactylation toward effective cancer control. This review underpins important yet less-studied area in histone lactylation, and sheds insights on its clinical impact as well as possible therapeutic tools targeting lactylation.

Keywords

Cancerepigenesishallmarkhistone lactylationlactatetherapeutic translation

Information

Type
Review
Information
Expert Reviews in Molecular Medicine , Volume 25 , 2023 , e7
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Copyright
Copyright © The Author(s), 2023. Published by Cambridge University Press

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Footnotes

*

These authors contribute equally to this work.

References

de la Cruz Munoz-Centeno, M, Millan-Zambrano, G and Chavez, S (2012) A matter of packaging: influence of nucleosome positioning on heterologous gene expression. Methods in Molecular Biology 824, 51–64.CrossRefGoogle ScholarPubMed
Mikkelsen, TS et al. (2007) Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature 448, 553–560.CrossRefGoogle Scholar
Bernstein, BE, Meissner, A and Lander, ES (2007) The mammalian epigenome. Cell 128, 669–681.CrossRefGoogle ScholarPubMed
Zhang, D et al. (2019) Metabolic regulation of gene expression by histone lactylation. Nature 574, 575–580.CrossRefGoogle ScholarPubMed
Yu, J et al. (2021) Histone lactylation drives oncogenesis by facilitating m(6)A reader protein YTHDF2 expression in ocular melanoma. Genome Biology 22, 85.CrossRefGoogle ScholarPubMed
Jiang, J et al. (2021) Lactate modulates cellular metabolism through histone lactylation-mediated gene expression in non-small cell lung cancer. Frontiers in Oncology 11, 647559.CrossRefGoogle ScholarPubMed
Hua, G et al. (2014) Targeting glucose metabolism in chondrosarcoma cells enhances the sensitivity to doxorubicin through the inhibition of lactate dehydrogenase-A. Oncology Reports 31, 2727–2734.CrossRefGoogle ScholarPubMed
Cui, H et al. (2021) Lung myofibroblasts promote macrophage profibrotic activity through lactate-induced histone lactylation. American Journal of Respiratory Cell and Molecular Biology 64, 115–125.CrossRefGoogle ScholarPubMed
Meng, X et al. (2021) Comprehensive analysis of lysine lactylation in rice (Oryza sativa) grains. Journal of Agricultural and Food Chemistry 69, 8287–8297.CrossRefGoogle ScholarPubMed
Nikooie, R, Moflehi, D and Zand, S (2021) Lactate regulates autophagy through ROS-mediated activation of ERK1/2/m-TOR/p-70S6K pathway in skeletal muscle. Journal of Cell Communication and Signaling 15, 107–123.CrossRefGoogle ScholarPubMed
Matejovic, M, Radermacher, P and Fontaine, E (2007) Lactate in shock: a high-octane fuel for the heart? Intensive Care Medicine 33, 406–408.CrossRefGoogle Scholar
Dienel, GA (2014) Lactate shuttling and lactate use as fuel after traumatic brain injury: metabolic considerations. Journal of Cerebral Blood Flow & Metabolism 34, 1736–1748.CrossRefGoogle ScholarPubMed
Bonuccelli, G et al. (2010) Ketones and lactate “fuel” tumor growth and metastasis: evidence that epithelial cancer cells use oxidative mitochondrial metabolism. Cell Cycle 9, 3506–3514.CrossRefGoogle ScholarPubMed
Haas, R et al. (2016) Intermediates of metabolism: from bystanders to signalling molecules. Trends in Biochemical Sciences 41, 460–471.CrossRefGoogle ScholarPubMed
Lee, TY (2021) Lactate: a multifunctional signaling molecule. Yeungnam University Journal of Medicine 38, 183–193.CrossRefGoogle ScholarPubMed
Ahmed, K et al. (2010) An autocrine lactate loop mediates insulin-dependent inhibition of lipolysis through GPR81. Cell Metabolism 11, 311–319.CrossRefGoogle ScholarPubMed
Weinreich, J et al. (2011) Rapamycin-induced impaired wound healing is associated with compromised tissue lactate accumulation and extracellular matrix remodeling. European Surgical Research 47, 39–44.CrossRefGoogle ScholarPubMed
Jha, MK and Morrison, BM (2020) Lactate transporters mediate Glia-neuron metabolic crosstalk in homeostasis and disease. Frontiers in Cellular Neuroscience 14, 589582.CrossRefGoogle ScholarPubMed
Jain, M et al. (2020) A D-lactate dehydrogenase from rice is involved in conferring tolerance to multiple abiotic stresses by maintaining cellular homeostasis. Scientific Reports 10, 12835.CrossRefGoogle Scholar
Vaupel, P and Multhoff, G (2021) The Warburg effect: historical dogma versus current rationale. Advances in Experimental Medicine and Biology 1269, 169–177.CrossRefGoogle ScholarPubMed
Chen, J et al. (2020) Warburg effect is a cancer immune evasion mechanism against macrophage immunosurveillance. Frontiers in Immunology 11, 621757.CrossRefGoogle ScholarPubMed
Kes, MMG et al. (2020) Oncometabolites lactate and succinate drive pro-angiogenic macrophage response in tumors. Biochimica et Biophysica Acta, Reviews on Cancer 1874, 188427.CrossRefGoogle ScholarPubMed
Vlachostergios, PJ et al. (2015) Elevated lactic acid is a negative prognostic factor in metastatic lung cancer. Cancer Biomarkers: Section A of Disease Markers 15, 725–734.CrossRefGoogle ScholarPubMed
Sonveaux, P et al. (2012) Targeting the lactate transporter MCT1 in endothelial cells inhibits lactate-induced HIF-1 activation and tumor angiogenesis. PLoS ONE 7, e33418.CrossRefGoogle ScholarPubMed
Cheung, SM et al. (2020) Lactate concentration in breast cancer using advanced magnetic resonance spectroscopy. British Journal of Cancer 123, 261–267.CrossRefGoogle ScholarPubMed
Hui, S et al. (2017) Glucose feeds the TCA cycle via circulating lactate. Nature 551, 115–118.CrossRefGoogle ScholarPubMed
Nelson, SJ et al. (2013) Metabolic imaging of patients with prostate cancer using hyperpolarized [1-(1)(3)C]pyruvate. Science Translational Medicine 5, 198–108.CrossRefGoogle Scholar
San-Millan, I and Brooks, GA (2017) Reexamining cancer metabolism: lactate production for carcinogenesis could be the purpose and explanation of the Warburg effect. Carcinogenesis 38, 119–133.Google ScholarPubMed
Izzo, LT and Wellen, KE (2019) Histone lactylation links metabolism and gene regulation. Nature 574, 492–493.CrossRefGoogle ScholarPubMed
Chen, AN et al. (2021) Lactylation, a novel metabolic reprogramming code: current Status and prospects. Frontiers in Immunology 12, 688910.CrossRefGoogle ScholarPubMed
Varner, EL et al. (2020) Quantification of lactoyl-CoA (lactyl-CoA) by liquid chromatography mass spectrometry in mammalian cells and tissues. Open Biology 10, 200187.CrossRefGoogle ScholarPubMed
Wang, T et al. (2021) Acetylation of lactate dehydrogenase B drives NAFLD progression by impairing lactate clearance. Journal of Hepatology 74, 1038–1052.CrossRefGoogle ScholarPubMed
Hanahan, D and Weinberg, RA (2000) The hallmarks of cancer. Cell 100, 57–70.CrossRefGoogle ScholarPubMed
Hanahan, D and Weinberg, RA (2011) Hallmarks of cancer: the next generation. Cell 144, 646–674.CrossRefGoogle ScholarPubMed
Colegio, OR et al. (2014) Functional polarization of tumour-associated macrophages by tumour-derived lactic acid. Nature 513, 559–563.CrossRefGoogle ScholarPubMed
Geissmann, F et al. (2010) Development of monocytes, macrophages, and dendritic cells. Science 327, 656–661.CrossRefGoogle ScholarPubMed
Wynn, TA, Chawla, A and Pollard, JW (2013) Macrophage biology in development, homeostasis and disease. Nature 496, 445–455.CrossRefGoogle ScholarPubMed
Irizarry-Caro, RA et al. (2020) TLR signaling adapter BCAP regulates inflammatory to reparatory macrophage transition by promoting histone lactylation. Proceedings of the National Academy of Sciences of the USA 117, 30628–30638.CrossRefGoogle ScholarPubMed
Ivashkiv, LB (2020) The hypoxia-lactate axis tempers inflammation. Nature Reviews Immunology 20, 85–86.CrossRefGoogle ScholarPubMed
Dichtl, S et al. (2021) Lactate and IL6 define separable paths of inflammatory metabolic adaptation. Science Advances 7, 3505.CrossRefGoogle ScholarPubMed
Siska, PJ et al. (2020) The immunological Warburg effect: can a metabolic-tumor-stroma score (MeTS) guide cancer immunotherapy? Immunological Reviews 295, 187–202.CrossRefGoogle ScholarPubMed
Brand, A et al. (2016) LDHA-Associated lactic acid production blunts tumor immunosurveillance by T and NK cells. Cell Metabolism 24, 657–671.CrossRefGoogle Scholar
Harmon, C et al. (2019) Lactate-mediated acidification of tumor microenvironment induces apoptosis of liver-resident NK cells in colorectal liver metastasis. Cancer Immunology Research 7, 335–346.CrossRefGoogle ScholarPubMed
Gottfried, E et al. (2006) Tumor-derived lactic acid modulates dendritic cell activation and antigen expression. Blood 107, 2013–2021.CrossRefGoogle ScholarPubMed
Husain, Z et al. (2013) Tumor-derived lactate modifies antitumor immune response: effect on myeloid-derived suppressor cells and NK cells. Journal of Immunology 191, 1486–1495.CrossRefGoogle ScholarPubMed
Zhou, Y et al. (2019) P53/lactate dehydrogenase A axis negatively regulates aerobic glycolysis and tumor progression in breast cancer expressing wild-type p53. Cancer Science 110, 939–949.CrossRefGoogle ScholarPubMed
Boidot, R et al. (2012) Regulation of monocarboxylate transporter MCT1 expression by p53 mediates inward and outward lactate fluxes in tumors. Cancer Research 72, 939–948.CrossRefGoogle ScholarPubMed
Liu, CL et al. (2009) Lactate inhibits lipolysis in fat cells through activation of an orphan G-protein-coupled receptor, GPR81. Journal of Biological Chemistry 284, 2811–2822.CrossRefGoogle ScholarPubMed
Moussaieff, A et al. (2015) Glycolysis-mediated changes in acetyl-CoA and histone acetylation control the early differentiation of embryonic stem cells. Cell Metabolism 21, 392–402.CrossRefGoogle ScholarPubMed
Hadzic, A et al. (2020) The lactate receptor HCA1 Is present in the choroid plexus, the Tela Choroidea, and the Neuroepithelial lining of the dorsal part of the third ventricle. International Journal of Molecular Sciences 21, 6451.CrossRefGoogle ScholarPubMed
Luo, F et al. (2017) Enhanced glycolysis, regulated by HIF-1alpha via MCT-4, promotes inflammation in arsenite-induced carcinogenesis. Carcinogenesis 38, 615–626.CrossRefGoogle ScholarPubMed
Garcia, CK et al. (1994) Molecular characterization of a membrane transporter for lactate, pyruvate, and other monocarboxylates: implications for the Cori cycle. Cell 76, 865–873.CrossRefGoogle ScholarPubMed
Khatib-Massalha, E et al. (2020) Lactate released by inflammatory bone marrow neutrophils induces their mobilization via endothelial GPR81 signaling. Nature Communications 11, 3547.CrossRefGoogle ScholarPubMed
Faubert, B et al. (2017) Lactate metabolism in human lung tumors. Cell 171, 358–371. e9.CrossRefGoogle ScholarPubMed
Pivovarova, AI and MacGregor, GG (2018) Glucose-dependent growth arrest of leukemia cells by MCT1 inhibition: feeding Warburg's sweet tooth and blocking acid export as an anticancer strategy. Biomedicine & Pharmacotherapy 98, 173–179.CrossRefGoogle ScholarPubMed
Saulle, E et al. (2020) Targeting lactate metabolism by inhibiting MCT1 or MCT4 impairs leukemic cell proliferation, induces two different related death-pathways and increases chemotherapeutic sensitivity of acute myeloid leukemia cells. Frontiers in Oncology 10, 621458.CrossRefGoogle ScholarPubMed
Todenhofer, T et al. (2018) Selective inhibition of the lactate transporter MCT4 reduces growth of invasive bladder cancer. Molecular Cancer Therapeutics 17, 2746–2755.CrossRefGoogle ScholarPubMed
Xie, Q et al. (2020) A lactate-induced snail/STAT3 pathway drives GPR81 expression in lung cancer cells. Biochimica et Biophysica Acta, Molecular Basis of Disease 1866, 165576.CrossRefGoogle ScholarPubMed
Brown, TP et al. (2020) The lactate receptor GPR81 promotes breast cancer growth via a paracrine mechanism involving antigen-presenting cells in the tumor microenvironment. Oncogene 39, 3292–3304.CrossRefGoogle Scholar
Haaga, JR and Haaga, R (2013) Acidic lactate sequentially induced lymphogenesis, phlebogenesis, and arteriogenesis (ALPHA) hypothesis: lactate-triggered glycolytic vasculogenesis that occurs in normoxia or hypoxia and complements the traditional concept of hypoxia-based vasculogenesis. Surgery 154, 632–637.CrossRefGoogle ScholarPubMed
Vallee, A, Guillevin, R and Vallee, JN (2018) Vasculogenesis and angiogenesis initiation under normoxic conditions through Wnt/beta-catenin pathway in gliomas. Reviews in the Neurosciences 29, 71–91.CrossRefGoogle ScholarPubMed
Lu, H, Forbes, RA and Verma, A (2002) Hypoxia-inducible factor 1 activation by aerobic glycolysis implicates the Warburg effect in carcinogenesis. Journal of Biological Chemistry 277, 23111–23115.CrossRefGoogle ScholarPubMed
Vegran, F et al. (2011) Lactate influx through the endothelial cell monocarboxylate transporter MCT1 supports an NF-kappaB/IL-8 pathway that drives tumor angiogenesis. Cancer Research 71, 2550–2560.CrossRefGoogle ScholarPubMed
Webb, BA et al. (2011) Dysregulated pH: a perfect storm for cancer progression. Nature Reviews Cancer 11, 671–677.CrossRefGoogle Scholar
Busco, G et al. (2010) NHE1 Promotes invadopodial ECM proteolysis through acidification of the peri-invadopodial space. FASEB Journal 24, 3903–3915.CrossRefGoogle ScholarPubMed
Walenta, S and Mueller-Klieser, WF (2004) Lactate: mirror and motor of tumor malignancy. Seminars in Radiation Oncology 14, 267–274.CrossRefGoogle ScholarPubMed
Baumann, F et al. (2009) Lactate promotes glioma migration by TGF-beta2-dependent regulation of matrix metalloproteinase-2. Neuro-Oncology 11, 368–380.CrossRefGoogle ScholarPubMed
Zhu, X et al. (2020) Lactate induced up-regulation of KLHDC8A (Kelch domain-containing 8A) contributes to the proliferation, migration and apoptosis of human glioma cells. Journal of Cellular and Molecular Medicine 24, 11691–11702.CrossRefGoogle Scholar
Ippolito, L et al. (2019) Cancer-associated fibroblasts promote prostate cancer malignancy via metabolic rewiring and mitochondrial transfer. Oncogene 38, 5339–5355.CrossRefGoogle ScholarPubMed
Goetze, K et al. (2011) Lactate enhances motility of tumor cells and inhibits monocyte migration and cytokine release. International Journal of Oncology 39, 453–463.Google ScholarPubMed
Yue, J et al. (2021) LncRNAs link cancer stemness to therapy resistance. American Journal of Cancer Research 11, 1051–1068.Google ScholarPubMed
Lopez-Menendez, C et al. (2021) E2A modulates stemness, metastasis, and therapeutic resistance of breast cancer. Cancer Research 81, 4529–4544.CrossRefGoogle ScholarPubMed
Cascone, T et al. (2018) Increased tumor glycolysis characterizes immune resistance to adoptive T cell therapy. Cell Metabolism 27, 977–987. e4.CrossRefGoogle ScholarPubMed
Taylor, S et al. (2015) Microenvironment acidity as a major determinant of tumor chemoresistance: proton pump inhibitors (PPIs) as a novel therapeutic approach. Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy 23, 69–78.CrossRefGoogle Scholar
Adar, Y et al. (2012) Imidazoacridinone-dependent lysosomal photodestruction: a pharmacological Trojan horse approach to eradicate multidrug-resistant cancers. Cell Death & Disease 3, e293.CrossRefGoogle ScholarPubMed
De Milito, A and Fais, S (2005) Tumor acidity, chemoresistance and proton pump inhibitors. Future Oncology 1, 779–786.CrossRefGoogle ScholarPubMed
Ellegaard, AM et al. (2013) Sunitinib and SU11652 inhibit acid sphingomyelinase, destabilize lysosomes, and inhibit multidrug resistance. Molecular Cancer Therapeutics 12, 2018–2030.CrossRefGoogle ScholarPubMed
Jansen, G et al. (1999) Multiple mechanisms of resistance to polyglutamatable and lipophilic antifolates in mammalian cells: role of increased folylpolyglutamylation, expanded folate pools, and intralysosomal drug sequestration. Molecular Pharmacology 55, 761–769.Google ScholarPubMed
Mahoney, BP et al. (2003) Tumor acidity, ion trapping and chemotherapeutics. I. Acid pH affects the distribution of chemotherapeutic agents in vitro. Biochemical Pharmacology 66, 1207–1218.CrossRefGoogle ScholarPubMed
Wojtkowiak, JW et al. (2011) Drug resistance and cellular adaptation to tumor acidic pH microenvironment. Molecular Pharmaceutics 8, 2032–2038.CrossRefGoogle ScholarPubMed
Federici, C et al. (2014) Exosome release and low pH belong to a framework of resistance of human melanoma cells to cisplatin. PLoS ONE 9, e88193.CrossRefGoogle Scholar
Apicella, M et al. (2018) Increased lactate secretion by cancer cells sustains non-cell-autonomous adaptive resistance to MET and EGFR targeted therapies. Cell Metabolism 28, 848–865. e6.CrossRefGoogle ScholarPubMed
Soni, VK et al. (2020) Curcumin circumvent lactate-induced chemoresistance in hepatic cancer cells through modulation of hydroxycarboxylic acid receptor-1. International Journal of Biochemistry & Cell Biology 123, 105752.CrossRefGoogle ScholarPubMed
Tang, L et al. (2018) Role of metabolism in cancer cell radioresistance and radiosensitization methods. Journal of Experimental & Clinical Cancer Research: CR 37, 87.CrossRefGoogle ScholarPubMed
Taddei, ML et al. (2020) Lactate in sarcoma microenvironment: much more than just a waste product. Cells 9, 102–109.CrossRefGoogle ScholarPubMed
Sattler, UG et al. (2010) Glycolytic metabolism and tumour response to fractionated irradiation. Radiotherapy & Oncology 94, 102–109.CrossRefGoogle ScholarPubMed
Koukourakis, MI et al. (2009) Lactate dehydrogenase 5 expression in squamous cell head and neck cancer relates to prognosis following radical or postoperative radiotherapy. Oncology 77, 285–292.CrossRefGoogle ScholarPubMed
Koukourakis, MI et al. (2011) Prognostic and predictive role of lactate dehydrogenase 5 expression in colorectal cancer patients treated with PTK787/ZK 222584 (vatalanib) antiangiogenic therapy. Clinical Cancer Research 17, 4892–4900.CrossRefGoogle ScholarPubMed
Koukourakis, MI et al. (2014) Lactate dehydrogenase 5 isoenzyme overexpression defines resistance of prostate cancer to radiotherapy. British Journal of Cancer 110, 2217–2223.CrossRefGoogle ScholarPubMed
Koncosova, M et al. (2021) Inhibition of mitochondrial metabolism leads to selective eradication of cells adapted to acidic microenvironment. International Journal of Molecular Sciences 22, 594743.CrossRefGoogle ScholarPubMed
Gao, M, Zhang, N and Liang, W (2020) Systematic analysis of lysine lactylation in the plant fungal pathogen Botrytis cinerea. Frontiers in Microbiology 11, 594743.CrossRefGoogle ScholarPubMed
Bhagat, TD et al. (2019) Lactate-mediated epigenetic reprogramming regulates formation of human pancreatic cancer-associated fibroblasts. Elife 8, 5091.CrossRefGoogle ScholarPubMed
Zhang, M et al. (2021) Ten-eleven translocation 1 mediated-DNA hydroxymethylation is required for myelination and remyelination in the mouse brain. Nature Communications 12, 5091.CrossRefGoogle ScholarPubMed
Sulkowski, PL et al. (2017) 2-Hydroxyglutarate produced by neomorphic IDH mutations suppresses homologous recombination and induces PARP inhibitor sensitivity. Science Translational Medicine 9, 20188–20197.CrossRefGoogle ScholarPubMed
Nadtochiy, SM et al. (2016) Acidic pH is a metabolic switch for 2-hydroxyglutarate generation and signaling. Journal of Biological Chemistry 291, 20188–20197.CrossRefGoogle ScholarPubMed
Genders, AJ et al. (2019) A physiological drop in pH decreases mitochondrial respiration, and HDAC and Akt signaling, in L6 myocytes. American Journal of Physiology. Cell Physiology 316, C404–C414.CrossRefGoogle ScholarPubMed
Chisolm, DA and Weinmann, AS (2018) Connections between metabolism and epigenetics in programming cellular differentiation. Annual Review of Immunology 36, 221–246.CrossRefGoogle ScholarPubMed
Dai, X et al. (2021) Histone lactylation: epigenetic mark of glycolytic switch. Trends in Genetics 38, 124–127.CrossRefGoogle ScholarPubMed
Feng, J et al. (2017) Tumor cell-derived lactate induces TAZ-dependent upregulation of PD-L1 through GPR81 in human lung cancer cells. Oncogene 36, 5829–5839.CrossRefGoogle ScholarPubMed
Feichtinger, RG and Lang, R (2019) Targeting L-lactate metabolism to overcome resistance to immune therapy of melanoma and other tumor entities. Journal of Oncology 2019, 2084195.CrossRefGoogle ScholarPubMed
Allison, SJ et al. (2014) Identification of LDH-A as a therapeutic target for cancer cell killing via (i) p53/NAD(H)-dependent and (ii) p53-independent pathways. Oncogenesis 3, e102.CrossRefGoogle Scholar
Huang, C et al. (2020) A screened GPR1 peptide exerts antitumor effects on triple-negative breast cancer. Molecular Therapy Oncolytics 18, 602–612.CrossRefGoogle ScholarPubMed
de Boer, VC and Houten, SM (2014) A mitochondrial expatriate: nuclear pyruvate dehydrogenase. Cell 158, 9–10.CrossRefGoogle ScholarPubMed
Dong, G et al. (2016) Diisopropylamine dichloroacetate enhances radiosensitization in esophageal squamous cell carcinoma by increasing mitochondria-derived reactive oxygen species levels. Oncotarget 7, 68170–68178.CrossRefGoogle ScholarPubMed
Bonnet, S et al. (2007) A mitochondria-K + channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth. Cancer Cell 11, 37–51.CrossRefGoogle ScholarPubMed
Powell, SF et al. (2022) Phase II study of dichloroacetate, an inhibitor of pyruvate dehydrogenase, in combination with chemoradiotherapy for unresected, locally advanced head and neck squamous cell carcinoma. Investigational New Drugs 40, 622–633.CrossRefGoogle ScholarPubMed
Su, L et al. (2016) Superior anti-tumor efficacy of diisopropylamine dichloroacetate compared with dichloroacetate in a subcutaneous transplantation breast tumor model. Oncotarget 7, 65721–65731.CrossRefGoogle Scholar
Davids, MS et al. (2021) A phase 1b/2 study of duvelisib in combination with FCR (DFCR) for frontline therapy for younger CLL patients. Leukemia 35, 1064–1072.CrossRefGoogle ScholarPubMed
Dai, X et al. (2018) The emerging role of gas plasma in oncotherapy. Trends in Biotechnology 36, 1183–1198.CrossRefGoogle ScholarPubMed
Pajak, B et al. (2019) 2-Deoxy-d-glucose and its analogs: from diagnostic to therapeutic agents. International Journal of Molecular Sciences 21(1), 234.CrossRefGoogle ScholarPubMed
Li, W et al. (2017) Benserazide, a dopadecarboxylase inhibitor, suppresses tumor growth by targeting hexokinase 2. Journal of Experimental & Clinical Cancer Research 36(1), 58.CrossRefGoogle ScholarPubMed
Zhang, Q et al. (2014) Hexokinase II inhibitor, 3-BrPA induced autophagy by stimulating ROS formation in human breast cancer cells. Genes and Cancer 5(3-4), 100–112.CrossRefGoogle ScholarPubMed
Kim, DJ et al. (2019) Tristetraprolin-mediated hexokinase 2 expression regulation contributes to glycolysis in cancer cells. Molecular Biology of the Cell 30(5), 542–553.CrossRefGoogle ScholarPubMed
An, MX et al. (2017) BAG3 directly stabilizes Hexokinase 2 mRNA and promotes aerobic glycolysis in pancreatic cancer cells. Journal of Cell Biology 216(12), 4091–4105.CrossRefGoogle ScholarPubMed