Modulation of Immuno-biome during Radio-sensitization of Tumors by Glycolytic Inhibitors

Current Medicinal Chemistry
Seema Gupta, B S Dwarakanath

Abstract

The Tumor Microenvironment (TME) comprising stromal cells, fibroblasts and various components of the immune system forms a pro-tumorigenic cocoon around the tumor cells with the reprogramming of the metabolism in the form of Warburg phenotype (enhanced aerobic glycolysis) in tumor as well as non-tumor cells. This reprogramming plays a significant role in suppressing the immune response leading to the survival and proliferation of tumor cells and resistance to therapies. Therefore, there is a considerable interest in developing strategies involving metabolic modifiers to improve the therapeutic efficacy that restores immune competence, besides enhancing the direct effects on tumor cells. Inhibitors of glycolysis like 2-deoxy-D-glucose (2-DG; a hexokinase inhibitor), dichloroacetate and small molecule inhibitors of lactate transport (MCT-1) are some of the metabolic modifiers investigated for their therapeutic as well as adjuvant potential. Among these, 2-DG has been widely investigated and established as an ideal adjuvant in the radio- and chemotherapy of tumors. Modulation of the immuno-biome in the form of cytokine shifts, differential transcriptional regulation, abrogation of immunosuppressive network and reduced accumulation...Continue Reading

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May 28, 2019·Journal of Experimental & Clinical Cancer Research : CR·Jinguan LinQianjin Liao
Dec 13, 2019·Oxidative Medicine and Cellular Longevity·Tiziana Tataranni, Claudia Piccoli
Jul 25, 2021·International Journal of Molecular Sciences·Kristina M CookEric Hau

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