Title : Molecular pathogenesis of IBD associated colon cancer
Abstract:
The inflammatory bowel diseases (IBD) are chronic inflammatory diseases of the gastrointestinal tract, and are associated with an elevated rate of developing colitis-associated colorectal cancer (CAC). Although the precise etiology and pathogenesis of CAC are not completely understood, it is now believed that several factors could contribute to the development of CAC, including chronic inflammation, immune dysregulation and gut microbial dysbiosis. Compared to sporadic colorectal cancer (CRC), CAC arises in a chronically inflamed mucosa, in which the colon epithelium undergoes repeated cycles of inflammation and tissue repair, resulting in oxidative stress and accumulation of reactive oxidative species (ROS). Excessive ROS causes oxidative stress and damage to DNA, proteins and lipids, leading to tumor initiation. While sporadic CRC typically develops from polyps to early adenoma and progress to invasive carcinoma, CAC usually arises from flat dysplastic mucosa and progresses in a step-wise fashion from negative for dysplasia to low-grade dysplasia to High-grade dysplasia to carcinoma. Genetics and epigenetic analyses of CAC and animal models of chronic GI inflammation have shown that molecular alterations of CAC are distinct from sporadic CRC. This presentation will first review the current understanding of the molecular pathogenesis of CAC, followed by discussion of ongoing studies in our lab in genomic and proteomic characterization of CAC and its precursors to elucidate the pathogenesis and develop diagnostic biomarkers and therapeutic targets. Finally, we will discuss tumor necrosis factor receptor-associated protein 1 (TRAP1), a CAC biomarker, as a potential diagnostic and therapeutic target for CAC.
Audience Take Away:
- Update on the molecular pathogenesis of colitis-associated colorectal cancer.
- Understand the molecular characteristics that are specific to colitis-associated colorectal cancer.
- Understand how chronic inflammation promote CAC development.
- Better understanding of the mechanisms could lead to new insights in developing diagnostic and therapeutic targets for prevention, early detection and treatment of CAC.
