Published online Jul 15, 2023. doi: 10.4239/wjd.v14.i7.977
Peer-review started: January 9, 2023
First decision: January 17, 2023
Revised: January 31, 2023
Accepted: April 17, 2023
Article in press: April 17, 2023
Published online: July 15, 2023
Processing time: 184 Days and 15.6 Hours
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.
Core Tip: The receptor for advanced glycation products (RAGE) is involved in every stage of the pathophysiological pathways that lead to the progression of obesity, type 2 diabetes, and cancer. This article provides a focused discussion on the stages of obesity leading to the development of metabolic diseases and provides a broad overview of the contribution of RAGE to the development of diabetes and cancer.