Targeting Chronic Inflammation of the Digestive System in Cancer Prevention: Modulators of the Bioactive Sphingolipid Sphingosine-1-Phosphate Pathway
Central Laboratory, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, China
Guangdong Provincial Engineering Research Center for Esophageal Cancer Precise Therapy, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, China
School of Life Sciences, University of Technology Sydney, Broadway, Sydney, NSW 2007, Australia
Author to whom correspondence should be addressed.
Academic Editor: Olga Sukocheva
Received: 13 December 2021
Revised: 15 January 2022
Accepted: 18 January 2022
Published: 21 January 2022
Obesity, an ongoing global pandemic, is a major contributor to inflammation and cancers of the digestive system. High saturated fat diets and being overweight are associated with chronic inflammation and increased cancer risk. Signalling molecules made from saturated fats known as bioactive sphingolipids play essential roles in healthy gastrointestinal immunity. In excess, these sphingolipid molecules can compromise our immune system leading to chronic, low-grade inflammation within the digestive system preceding many metabolic diseases including cancer. Sphingosine-1-phosphate is a bioactive sphingolipid and, in excess, contributes to chronic inflammation. Drugs that block sphingosine-1-phosphate activity have the potential to prevent chronic inflammation and reduce gastrointestinal cancer risk. We review how disruption of the sphingosine-1-phosphate pathway contributes to gastrointestinal inflammation and cancer. We also discuss the use of modulators of the sphingospine-1-phosphate pathway in clinical trials and in the clinic as therapeutics for inflammatory gastrointestinal diseases with the benefit of reducing cancer risk.