2 型糖尿病 (T2DM) 与乳腺癌风险增加之间的联系促使人们探索针对共享代谢途径的新治疗策略。本综述重点关注钠-葡萄糖协同转运蛋白 2 (SGLT2) 抑制剂在乳腺癌中潜在抗癌作用的新证据。临床前研究表明，多种SGLT2抑制剂，如卡格列净、达格列净、伊格列净和恩格列净，可以抑制乳腺癌细胞增殖、诱导细胞凋亡、调节关键细胞信号通路。这些机制包括激活 AMP 激活蛋白激酶 (AMPK)、抑制哺乳动物雷帕霉素靶点 (mTOR) 信号传导以及调节脂质代谢和炎症介质。 SGLT2抑制剂与常规治疗（包括化疗和放疗）以及磷酸肌醇3激酶（PI3K）抑制剂等靶向治疗的结合，在增强抗癌功​​效和潜在减少治疗相关毒性方面显示出有希望的结果。预测对 SGLT2 抑制剂治疗的反应性的特定生物标志物或遗传特征的鉴定可以实现更加个性化的治疗选择和优化，特别是对于具有挑战性的乳腺癌亚型[例如，三阴性乳腺癌（TNBC）]。正在进行和未来的临床试验研究 SGLT2 抑制剂的使用，无论是作为单一疗法还是与其他药物联合使用，对于阐明其转化潜力并指导其纳入综合乳腺癌护理至关重要。总体而言，SGLT2 抑制剂代表了一种新颖且有前途的治疗方法，有可能改善各种乳腺癌亚型（包括侵袭性和化疗耐药性 TNBC）患者的临床结果。版权所有 © 2024。由 Elsevier B.V. 出版。

The link between type 2 diabetes mellitus (T2DM) and an increased risk of breast cancer has prompted the exploration of novel therapeutic strategies targeting shared metabolic pathways. This review focuses on the emerging evidence surrounding the potential anti-cancer effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors in the context of breast cancer. Preclinical studies have demonstrated that various SGLT2 inhibitors, such as canagliflozin, dapagliflozin, ipragliflozin, and empagliflozin, can inhibit the proliferation of breast cancer cells, induce apoptosis, and modulate key cellular signaling pathways. These mechanisms include the activation of AMP-activated protein kinase (AMPK), suppression of mammalian target of rapamycin (mTOR) signaling, and regulation of lipid metabolism and inflammatory mediators. The combination of SGLT2 inhibitors with conventional treatments, including chemotherapy and radiotherapy, as well as targeted therapies like phosphoinositide 3-kinases (PI3K) inhibitors, has shown promising results in enhancing the anti-cancer efficacy and potentially reducing treatment-related toxicities. The identification of specific biomarkers or genetic signatures that predict responsiveness to SGLT2 inhibitor therapy could enable more personalized treatment selection and optimization, particularly for challenging breast cancer subtypes [e, g., triple negative breast cancer (TNBC)]. Ongoing and future clinical trials investigating the use of SGLT2 inhibitors, both as monotherapy and in combination with other agents, will be crucial in elucidating their translational potential and guiding their integration into comprehensive breast cancer care. Overall, SGLT2 inhibitors represent a novel and promising therapeutic approach with the potential to improve clinical outcomes for patients with various subtypes of breast cancer, including the aggressive and chemo-resistant TNBC.Copyright © 2024. Published by Elsevier B.V.