肥胖症和2型糖尿病（T2DM）是全球高发病率的慢性病理状态。它们共享一些病理机制，包括高胰岛素血症、激素的产生和释放以及高血糖。以上所述病理过程会随着时间的推移影响人体其他系统，引起组织缺氧、低级别炎症和氧化应激，为癌症的发病奠定病理基础。全球死亡的主要原因是T2DM和癌症。这种病理三联体的其他主要改变包括高级糖基化终产物的积累，以及由于细胞死亡引起的内源性报警分子的释放（例如细胞内蛋白高迁移率盒蛋白1和蛋白S100），它们与高级糖基化产物受体（RAGE）结合，后者是涉及炎症、代谢和肿瘤过程的多配体受体。本综述分析了有关RAGE在肥胖、T2DM和癌症发展中的作用的最新研究报告，目的是了解与癌症起始相关的细胞内信号传导机制。本综述还探讨了炎症、氧化应激、缺氧、细胞衰老、RAGE配体、肿瘤微环境变化以及与T2DM相关的主要肿瘤的“癌症特征”。吸收这些信息有助于发展降低这些疾病发病率和死亡率的诊断和治疗方法。©作者2023年。由百世邦出版集团版权所有。

Obesity and type 2 diabetes mellitus (T2DM) are chronic pathologies with a high incidence worldwide. They share some pathological mechanisms, including hyperinsulinemia, the production and release of hormones, and hyperglycemia. The above, over time, affects other systems of the human body by causing tissue hypoxia, low-grade inflammation, and oxidative stress, which lay the pathophysiological groundwork for cancer. The leading causes of death globally are T2DM and cancer. Other main alterations of this pathological triad include the accumulation of advanced glycation end products and the release of endogenous alarmins due to cell death (i.e., damage-associated molecular patterns) such as the intracellular proteins high-mobility group box protein 1 and protein S100 that bind to the receptor for advanced glycation products (RAGE) - a multiligand receptor involved in inflammatory and metabolic and neoplastic processes. This review analyzes the latest advanced reports on the role of RAGE in the development of obesity, T2DM, and cancer, with an aim to understand the intracellular signaling mechanisms linked with cancer initiation. This review also explores inflammation, oxidative stress, hypoxia, cellular senescence, RAGE ligands, tumor microenvironment changes, and the "cancer hallmarks" of the leading tumors associated with T2DM. The assimilation of this information could aid in the development of diagnostic and therapeutic approaches to lower the morbidity and mortality associated with these diseases.©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.