Pathophysiology of colitis-associated colorectal cancer

Colitis-associated colorectal cancer (caCRC) is a subset of lower gastrointestinal tract malignancies that occurs in patients with inflammatory bowel disease (IBD), such as ulcerative colitis and Crohn's disease. The global prevalence of IBD is increasing, putting more individuals at risk of developing caCRC. The pathophysiological mechanisms that underlie the initiation and growth of caCRC remain to be fully elucidated. Nevertheless, studies have provided novel insights into the pathophysiology of caCRC, underscoring the distinguishing characteristics of caCRC compared with sporadic forms of CRC. In this Review, we describe the key mechanisms that drive caCRC. Starting from a clinical perspective and highlighting key features of the tumour epithelium, we discuss typical caCRC-related characteristics among subtypes of CRC, with a particular focus on the role of stromal cells in the tumour microenvironment. In addition, we review the contributions of immune cells to tumour control versus tumour promotion, and how signals from the gut microbiome might influence tumour development in caCRC. We also discuss various aspects of the pathophysiological heterogeneity of caCRC. Finally, we outline potential implications for therapy, and how these findings could be translated into future strategies of personalized medicine targeting caCRC.