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Tumor lactic acid: a potential target for cancer therapy

期刊

ARCHIVES OF PHARMACAL RESEARCH
卷 46, 期 2, 页码 90-110

出版社

PHARMACEUTICAL SOC KOREA
DOI: 10.1007/s12272-023-01431-8

关键词

Tumors; Lactic acid; Lactate dehydrogenases; Monocarboxylate transporters; Lactic acid blocking strategy; Anti-tumor therapy

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Tumor development is affected by circulating metabolites, with elevated levels of lactic acid and low levels of glucose and glutamine. Lactic acid, a major circulating carbon metabolite produced by tumors, regulates energy metabolism and cancer cell signaling pathways. Recent studies have identified the pro-tumorigenic action of lactic acid and propose targeting its metabolism as a therapeutic strategy for anti-cancer therapy.
Tumor development is influenced by circulating metabolites and most tumors are exposed to substantially elevated levels of lactic acid and low levels of nutrients, such as glucose and glutamine. Tumor-derived lactic acid, the major circulating carbon metabolite, regulates energy metabolism and cancer cell signaling pathways, while also acting as an energy source and signaling molecule. Recent studies have yielded new insights into the pro-tumorigenic action of lactic acid and its metabolism. These insights suggest an anti-tumor therapeutic strategy targeting the oncometabolite lactic acid, with the aim of improving the efficacy and clinical safety of tumor metabolism inhibitors. This review describes the current understanding of the multifunctional roles of tumor lactic acid, as well as therapeutic approaches targeting lactic acid metabolism, including lactate dehydrogenase and monocarboxylate transporters, for anti-cancer therapy.

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