Diabetes and Pancreatic Cancer—A Dangerous Liaison Relying on Carbonyl Stress
Department of Clinical and Molecular Medicine, “La Sapienza” University, 00189 Rome, Italy
Department of Neurosciences, Rehabilitation, Ophtalmology, Genetic and Maternal Infantile Sciences (DINOGMI), Department of Excellence of MIUR, University of Genoa Medical School, 16132 Genoa, Italy
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Received: 14 December 2020 / Revised: 9 January 2021 / Accepted: 14 January 2021 / Published: 16 January 2021
Diabetic people have an increased risk of developing several types of cancers, particularly pancreatic cancer. The higher availability of glucose and/or lipids that characterizes diabetes and obesity is responsible for the increased production of highly reactive carbonyl compounds, a condition referred to as “carbonyl stress”. Also known as glycotoxins and lipotoxins, these compounds react quickly and damage various molecules in cells forming final products termed AGEs (advanced glycation end-products). AGEs were shown to markedly accelerate tumor development in an experimental model of pancreatic cancer and AGE inhibition prevented the tumor-promoting effect of diabetes. In humans, carbonyl stress has been associated with the risk of pancreatic cancer and recognized as a possible contributor to other cancers, including breast and colorectal cancer. These findings suggest that carbonyl stress is involved in cancer development and growth and may be the mechanistic link between diabetes and pancreatic cancer, thus representing a potential drug target.