In metabolic conditions such as obesity and diabetes, which are associated with deregulated signaling of the insulin/insulin-like growth factor system (IIGFs), inflammation plays a dominant role. In cancer, IIGFs is implicated in disease progression, particularly during obesity and diabetes; however, further mediators may act in concert with IIGFs to trigger meta-inflammation. The receptor for advanced glycation end-products (RAGE) and its ligands bridge together metabolism and inflammation in obesity, diabetes, and cancer. Herein, we summarize the main mechanisms of meta-inflammation in malignancies associated with obesity and diabetes; we provide our readers with the most recent understanding and conceptual advances on the role of RAGE at the crossroad between impaired metabolism and inflammation, toward disease aggressiveness. We inform on the potential hubs of cross-communications driven by aberrant RAGE axis and dysfunctional IIGFs in the tumor microenvironment. Furthermore, we offer a rationalized view on the opportunity to terminate meta-inflammation via targeting RAGE pathway, and on the possibility to shut its molecular connections with IIGFs, toward a better control of diabetes- and obesity-associated cancers.

中文翻译：

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胰岛素/IGF 轴和高级糖基化终产物的受体：在元炎症中的作用和癌症治疗的潜力。

在肥胖和糖尿病等与胰岛素/胰岛素样生长因子系统（IIGF）信号失调相关的代谢疾病中，炎症起着主导作用。在癌症中，IIGF 与疾病进展有关，特别是在肥胖和糖尿病期间；然而，其他介质可能与 IIGF 协同作用，引发元炎症。晚期糖基化终末产物 (RAGE) 受体及其配体将肥胖、糖尿病和癌症中的代谢和炎症联系在一起。在此，我们总结了与肥胖和糖尿病相关的恶性肿瘤中元炎症的主要机制；我们为读者提供关于 RAGE 在代谢受损和炎症之间的十字路口的作用以及疾病侵袭性的最新理解和概念进展。我们介绍了肿瘤微环境中由异常 RAGE 轴和功能失调的 IIGF 驱动的潜在交叉通讯中心。此外，我们对通过靶向 RAGE 通路终止元炎症的机会，以及关闭其与 IIGF 分子联系的可能性，以更好地控制与糖尿病和肥胖相关的癌症提供了合理的观点。