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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 rightsided
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 â??malignant inflammatory profileâ?? Another area of active research is the influence of the intestinal flora,
the â??colonic microbiomeâ? on tumorigenesis. Studies suggest that disturbances in the composition, distribution and/or metabolism
(â??dysbiosisâ?) of the colonic microbiota may shift the homeostatic environment of the colon toward inflammation, dysplasia and
cancer. Is there a â??malignant microbial signatureâ?? Better understanding of how inflammation and dysbiosis promote tumorigenesis
may provide new strategies for prevention and treatment of colorectal cancer.