Insulin/IGF Axis and the Receptor for Advanced Glycation End Products: Role in Meta-inflammation and Potential in Cancer Therapy

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.

Automated summary

In metabolic conditions such as obesity and diabetes, inflammation plays a dominant role, particularly in cancer. The receptor for advanced glycation end-products (RAGE) and its ligands bridge metabolism and inflammation in these conditions. This article summarizes the mechanisms of meta-inflammation in obesity- and diabetes-associated cancers, focusing on the role of RAGE and impaired insulin/insulin-like growth factor system (IIGFs) signaling. It also discusses the potential to target the RAGE pathway and its molecular connections with IIGFs to better control these types of cancers.