Martine Claire McManus
Cleveland Clinic, Abu Dhabi
Title: Emerging Concepts in the Our Understanding of Colorectal Cancer
Biography
Biography: Martine Claire McManus
Abstract
Colorectal cancer is one of the most common cancers globally. Colonic adenocarcinoma is a straightforward diagnosis under the microscope, and its molecular progression from adenoma-to-carcinoma is well-defined and understood. We know that right-sided and left-sided colon cancers are often morphologically and biologically distinct. Right-sided tumors frequently show mucinous histology, usually have tumor-infiltrating lymphocytes, and progress along the microsatellite instability pathway. Lynch Syndrome is the prototypic right-sided tumor. Left-sided tumors, conversely, are rarely mucinous, do not demonstrate tumor-infiltrating lymphocytes, and progress along the chromosomal instability pathway. Familial Adenomatous Polyposis is the prototypic left-sided colon cancer syndrome. We know that signet-ring cell morphology is a negative prognostic indicator, and that tumor-infiltrating lymphocytes usually imply a better prognosis. Colonic carcinogenesis is dependent on complex interactions between the intestinal microenvironment and the host immune response. Insight into the tumor microenvironment is beginning to provide some of the potential mechanisms of tumorigenesis. Emerging concepts include elucidation of the role of inflammatory cells in tumorigenesis. How do inflammatory cells interact with tumor cells? Why do some inflammatory cells act to inhibit tumor growth while others are tumor-promoting? Is there a “malignant inflammatory profile”? Another area of active research is the influence of the intestinal flora, the “colonic microbiome” on tumorigenesis. Studies suggest that disturbances in the composition, distribution and/or metabolism (“dysbiosis”) of the colonic microbiota may shift the homeostatic environment of the colon toward inflammation, dysplasia and cancer. Is there a “malignant microbial signature”? Better understanding of how inflammation and dysbiosis promote tumorigenesis may provide new strategies for prevention and treatment of colorectal cancer.