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Lactate transporters as therapeutic targets in cancer and inflammatory diseases

机译：乳酸转运蛋白作为癌症和炎症性疾病的治疗靶标

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Introduction: Inflammation is associated with the accumulation of lactate at sites of tumor-growth and inflammation. Lactate initiates tissue-responses contributing to disease. We discuss the potential of targeting lactate transporters in the treatment of cancer and inflammatory conditions. Areas covered: Lactate is the end product of glycolysis, often considered a waste metabolite but also a fuel for oxidative cells. It is however an active signaling molecule with immunomodulatory and angiogenic properties. They are the consequence of lactate binding to membrane receptor(s) or being transported through specific carrier-mediated-transporters across the cellular membrane. Carriers are distinct in proton-linked-monocarboxylate-transporters (MCTs) and Na+-coupled- electro-genic-transporters, expressed by several tissues including immune-system, endothelium and epithelium. Several tumors and inflammatory sites show accumulation of lactate and altered expression of its transporters, thus suggesting a role of this metabolite in cancer and inflammation. We review the most recent evidence on lactate biology, focusing on transporter expression and function in health and disease. Expert opinion: Lactate-initiated signaling is gaining attention for its implications in cancer and inflammation. This review discusses the therapeutic potential of targeting lactate transporters and drugs that are already in clinical use for cancer and discusses the opportunity to develop new therapeutics for inflammation and cancer.
机译：简介：炎症与肿瘤生长和炎症位点的积累有关。乳酸乳酸乳酸乳酸症是有助于疾病的组织反应。我们讨论靶向乳酸转运蛋白的潜力在治疗癌症和炎症条件下。所涵盖的区域：乳酸是糖酵解的最终产物，通常被认为是废弃物代谢物，但也是氧化细胞的燃料。然而，它是具有免疫调节性和血管生成性质的活性信号分子。它们是乳酸与膜受体的结合或通过在细胞膜穿过细胞膜的特异性载体介导的转运蛋白的结果。载体在质子 - 连接 - 单羧酸盐 - 转运物（MCT）和Na + -coupled-电遗传转运蛋白中不同，由几种组织表示，包括免疫系统，内皮和上皮。几种肿瘤和炎症部位显示出乳酸的积累和转运蛋白的表达改变，表明这种代谢物在癌症和炎症中的作用。我们审查了关于乳酸生物学的最新证据，重点是在健康和疾病中的转运蛋白表达和功能。专家意见：乳酸发起的信令正在促使其对癌症和炎症的影响。本综述讨论了靶向乳酸转运蛋白和药物的治疗潜力，这些潜力已经在临床用途癌症中，并探讨了为炎症和癌症开发新治疗方法的机会。

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