Inflammation-associated genomic instability in cancer

Abstract

Inflammation is essential in protecting us against foreign pathogens. However when left unchecked, it becomes chronic inflammation, a potential precursor to carcinogenesis. While inflammatory signalling provides pro-survival stimuli, it also causes genomic instability and allows mutant cells to escape cell cycle arrest and apoptosis. This occurs through the release of reactive oxygen/nitrogen species (ROS/RNS), the increased expression of activation-induced cytidine deaminase (AID), inhibition of p53 function and the reactivation of TERT expression. Because chronic inflammation can ultimately lead to genomic instability, there is a need to target chronic inflammation, through the suppression of effector pathways with biologics or small molecules. More recently, therapies have also focused on stimulating physiological resolution, which offers a promising, tissue-specific alternative. As we better understand the triggers of chronic inflammation, therapies can be more specific, without compromising the overall functions of our immune system.