Diabetes Center, First Department of Propaedeutic Internal Medicine, Medical School, Laiko General Hospital, National and Kapustina University of Athens, 11527 Athens, Greece.
First Department of Internal Medicine, Sismanogleio General Hospital, 15126 Athens, Greece.
Biomolecules. 2024 Nov 20;14(11):1479. doi: 10.3390/biom14111479.
Diabetes mellitus (DM) is a significant risk factor for various cancers, with the impact of anti-diabetic therapies on cancer progression differing across malignancies. Among these therapies, metformin has gained attention for its potential anti-cancer effects, primarily through modulation of the AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) pathway and the induction of autophagy. Beyond metformin, other conventional anti-diabetic treatments, such as insulin, sulfonylureas (SUs), pioglitazone, and dipeptidyl peptidase-4 (DPP-4) inhibitors, have also been examined for their roles in cancer biology, though findings are often inconclusive. More recently, novel medications, like glucagon-like peptide-1 (GLP-1) receptor agonists, dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) agonists, and sodium-glucose co-transporter-2 (SGLT-2) inhibitors, have revolutionized DM management by not only improving glycemic control but also delivering substantial cardiovascular and renal benefits. Given their diverse metabolic effects, including anti-obesogenic properties, these novel agents are now under meticulous investigation for their potential influence on tumorigenesis and cancer advancement. This review aims to offer a comprehensive exploration of the evolving landscape of glucose-lowering treatments and their implications in cancer biology. It critically evaluates experimental evidence surrounding the molecular mechanisms by which these medications may modulate oncogenic signaling pathways and reshape the tumor microenvironment (TME). Furthermore, it assesses translational research and clinical trials to gauge the practical relevance of these findings in real-world settings. Finally, it explores the potential of anti-diabetic medications as adjuncts in cancer treatment, particularly in enhancing the efficacy of chemotherapy, minimizing toxicity, and addressing resistance within the framework of immunotherapy.
糖尿病（DM）是多种癌症的重要危险因素，不同恶性肿瘤的抗糖尿病治疗对癌症进展的影响也不同。在这些疗法中，二甲双胍因其潜在的抗癌作用而受到关注，主要通过调节 AMP 激活的蛋白激酶/雷帕霉素靶蛋白（AMPK/mTOR）途径和诱导自噬。除了二甲双胍，其他常规的抗糖尿病治疗方法，如胰岛素、磺酰脲类（SUs）、吡格列酮和二肽基肽酶-4（DPP-4）抑制剂，也因其在癌症生物学中的作用而被研究过，尽管研究结果往往不一致。最近，新型药物，如胰高血糖素样肽-1（GLP-1）受体激动剂、双重 GLP-1/葡萄糖依赖性胰岛素促分泌多肽（GIP）激动剂和钠-葡萄糖协同转运蛋白-2（SGLT-2）抑制剂，不仅通过改善血糖控制，而且通过提供实质性的心血管和肾脏益处，彻底改变了糖尿病的管理。鉴于它们具有不同的代谢作用，包括抗肥胖特性，这些新型药物目前正在进行细致的研究，以评估它们对肿瘤发生和癌症进展的潜在影响。本综述旨在全面探讨降糖治疗的不断发展的领域及其在癌症生物学中的意义。它批判性地评估了围绕这些药物可能调节致癌信号通路和重塑肿瘤微环境（TME）的分子机制的实验证据。此外，它评估了转化研究和临床试验，以评估这些发现在现实环境中的实际相关性。最后，它探讨了抗糖尿病药物作为癌症治疗辅助药物的潜力，特别是在增强化疗疗效、降低毒性和解决免疫治疗中的耐药性方面。
