Inflammation-Driven Colorectal Cancer Associated with Colitis: From Pathogenesis to Changing Therapy

SIMPLE SUMMARY: Patients with inflammatory bowel disease (IBD) are at an increased risk of developing colorectal cancer (CRC), mainly because of chronic intestinal inflammation. Some unique molecular differences occur in colitis-associated CRC, resulting in a different sequence of events, primarily of inflammation–dysplasia–carcinoma, compared to sporadic cases. In this context, the recent and continuous evolution in our understanding of the genetic and molecular mechanisms underlying IBD-associated CRC and the development of new OMIC techniques has opened up new possibilities for personalised and organ-sparing therapies. This review provides an overview of the IBD-related carcinogenesis pathway with a focus on the interaction between microbiota and the gut barrier and the role of currently available therapies for IBD in the inflammation–dysplasia–cancer sequence. ABSTRACT: Patients affected by inflammatory bowel disease (IBD) have a two-fold higher risk of developing colorectal cancer (CRC) than the general population. IBD-related CRC follows a different genetic and molecular pathogenic pathway than sporadic CRC and can be considered a complication of chronic intestinal inflammation. Since inflammation is recognised as an independent risk factor for neoplastic progression, clinicians strive to modulate and control disease, often using potent therapy agents to achieve mucosal healing and decrease the risk of colorectal cancer in IBD patients. Improved therapeutic control of inflammation, combined with endoscopic advances and early detection of pre-cancerous lesions through surveillance programs, explains the lower incidence rate of IBD-related CRC. In addition, current research is increasingly focused on translating emerging and advanced knowledge in microbiome and metagenomics into personalised, early, and non-invasive CRC screening tools that guide organ-sparing therapy in IBD patients. This review aims to summarise the existing literature on IBD-associated CRC, focusing on new insights into the alteration of the intestinal barrier and the interactions with the gut microbiome as the initial promoter. In addition, the role of OMIC techniques for precision medicine and the impact of the available IBD therapeutic armamentarium on the evolution to CRC will be discussed.