Pandey Aparamita, Alcaraz Martín, Saggese Pasquale, Soto Adriana, Gomez Estefany, Jaldu Shreya, Yanagawa Jane, Scafoglio Claudio
Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine, University of California Los Angeles, 700 Tiverton Drive, Los Angeles, CA 90095, USA.
Department of Biology and Biotechnologies Charles Darwin, University of Rome "Sapienza", Piazzale Aldo Moro 5, 00185 Rome, Italy.
Cancers (Basel). 2025 Jan 30;17(3):466. doi: 10.3390/cancers17030466.
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.
癌细胞比正常细胞消耗更多的葡萄糖，葡萄糖转运蛋白（GLUT）的表达是许多癌症已知的诊断靶点和预后因素。最近有证据表明，钠-葡萄糖转运蛋白也在不同类型的癌症中表达，而钠-葡萄糖协同转运蛋白2（SGLT2）引起了特别关注，因为目前有可阻断肾脏中SGLT2的抗糖尿病药物，这些药物可很容易地重新用于癌症治疗。本文的目的是对现有文献进行叙述性综述，并对SGLT2抑制剂在癌症治疗和预防中作用的证据进行批判性评估。SGLT2抑制剂可阻断近端肾小管中钠依赖的葡萄糖摄取，导致糖尿，并改善糖尿病患者的血糖水平和胰岛素敏感性。它们还具有一系列全身效应，包括降低血压、减轻体重和减轻炎症，这也使它们对心力衰竭和肾脏疾病有效。糖尿病患者的流行病学证据表明，接受SGLT2抑制剂治疗的个体患癌症的发病率可能较低，且预后较好。这些研究得到了临床前证据的证实，即在异种移植和基因工程模型中SGLT2抑制剂对癌症有作用，以及体外机制研究的证实。SGLT2抑制剂在癌症中的作用可通过直接抑制癌细胞对葡萄糖的摄取以及全身效应来介导。总之，有证据表明SGLT2抑制剂对不同类型的癌症可能有潜在作用。最有说服力的证据存在于肺腺癌、乳腺腺癌、肝细胞癌和胰腺癌中。几项正在进行的临床试验将提供更多关于SGLT2抑制剂抗癌疗效的信息。
