Cancer cells utilize larger amounts of glucose than their normal counterparts, and the expression of GLUT transporters is a known diagnostic target and a prognostic factor for many cancers. Recent evidence has shown that sodium-glucose transporters are also expressed in different types of cancer, and SGLT2 has raised particular interest because of the current availability of anti-diabetic drugs that block SGLT2 in the kidney, which could be readily re-purposed for the treatment of cancer. The aim of this article is to perform a narrative review of the existing literature and a critical appraisal of the evidence for a role of SGLT2 inhibitors for the treatment and prevention of cancer. SGLT2 inhibitors block Na-dependent glucose uptake in the proximal kidney tubules, leading to glycosuria and the improvement of blood glucose levels and insulin sensitivity in diabetic patients. They also have a series of systemic effects, including reduced blood pressure, weight loss, and reduced inflammation, which also make them effective for heart failure and kidney disease. Epidemiological evidence in diabetic patients suggests that individuals treated with SGLT2 inhibitors may have a lower incidence and better outcomes of cancer. These studies are confirmed by pre-clinical evidence of an effect of SGLT2 inhibitors against cancer in xenograft and genetically engineered models, as well as by in vitro mechanistic studies. The action of SGLT2 inhibitors in cancer can be mediated by the direct inhibition of glucose uptake in cancer cells, as well as by systemic effects. In conclusion, there is evidence suggesting a potential role of SGLT2 inhibitors against different types of cancer. The most convincing evidence exists for lung and breast adenocarcinomas, hepatocellular carcinoma, and pancreatic cancer. Several ongoing clinical trials will provide more information on the efficacy of SGLT2 inhibitors against cancer.
癌细胞相较于正常细胞消耗更多葡萄糖，葡萄糖转运蛋白（GLUT）的表达已成为多种癌症的诊断标志物和预后指标。最新研究表明钠-葡萄糖协同转运蛋白（SGLT）同样在多种癌症类型中表达，其中SGLT2因现有糖尿病治疗药物可特异性阻断肾脏SGLT2功能而备受关注，这类药物具有被重新用于癌症治疗的潜力。本文旨在系统评述现有文献，并对SGLT2抑制剂在癌症防治领域的证据进行批判性评估。SGLT2抑制剂通过阻断肾脏近端小管钠依赖性葡萄糖重吸收，诱导糖尿并改善糖尿病患者血糖水平与胰岛素敏感性。该类药物还具有降低血压、减轻体重、抑制炎症等全身效应，使其对心力衰竭和肾脏疾病亦具疗效。糖尿病患者流行病学数据显示，接受SGLT2抑制剂治疗的人群癌症发病率更低且预后更佳。异种移植模型、基因工程动物模型的临床前研究及体外机制实验进一步验证了这些发现。SGLT2抑制剂可能通过直接抑制癌细胞葡萄糖摄取及发挥全身效应双重机制作用于癌症。现有证据表明SGLT2抑制剂对多种癌症具有潜在防治作用，其中对肺腺癌、乳腺癌、肝细胞癌和胰腺癌的证据最为充分。多项正在进行中的临床试验将为SGLT2抑制剂的抗癌疗效提供更深入的数据支持。
Exploring the Role of SGLT2 Inhibitors in Cancer: Mechanisms of Action and Therapeutic Opportunities
肿瘤(癌症)患者之家