Update and latest advances in mechanisms and management of colitis-associated colorectal cancer

Figure 1 Different mechanisms of colitis-associated colorectal carcinogenesis. Recent advances underlying colitis-associated colorectal carcinogenesis include a variety of mechanisms, including genetics and epigenetics, immunity and inflammation, and microbiota. Their subtle and complex interactions contribute to the development of colorectal cancer (CAC): (1) DNA mutations, oxidative damage, DNA methylation and histone modifications promote colitis-associated colorectal carcinogenesis; (2) Classical signaling pathways such as NF-κB, Wnt/β-catenin, STAT3/IL-6 promote colitis-associated colorectal carcinogenesis. In addition, TIMs and macrophage polarization are also involved in carcinogenesis; and (3) Several bacteria (e.g., E. coli, ETBF, and Fn) and metabolites may cause DNA damage, inflammation, activation of several oncogenic signaling pathways and EMT, thereby promoting CAC. BFT: Bacteroides fragilis toxin; DSBs: Double-strand breaks; EMT: Epithelial-mesenchymal transition; E. coli: Escherichia coli; ETBF: Enterotoxigenic Bacteroides fragilis; Fn: Fusobacterium nucleatum; IKK: IκB kinase; MEL18: Polycomb group ring finger 2; NFATc3: Nuclear factor of activated T cells 3; NF-Κb: Nuclear factor-κB; ODC: Ornithine decarboxylase; PI3K: Phosphoinositide 3-kinase; Pou3f1: POU class 3 homeobox 1; STAT3: Signal transducer and activator of transcription 3; TIMs: Tumor-infiltrating myeloid cells; TLR4: Toll-like receptor 4.