Abstract

Colorectal cancer is the second most common cancer in both men and women. However colorectal cancer is not a single type of cancer. Its pathogenesis depends on the anatomical location of the tumor and differs from the right side and the left side of the colon. Tumors of the right-sided proximal colon and left-sided distal colon have different molecular and histological features. In right-sided tumors, mutations in the DNA mismatch repair pathway are commonly seen, and these tumors generally have flat histology. Mutations related to the chromosomal instability pathway such as APC, KRAS p53 are seen in left-sided tumors and these tumors demonstrate polypoid morphology. Responses to therapy are totally different among these tumor entities. Patients with left colorectal cancer benefit most from adjuvant chemotherapies such as 5-fluorouracil-based regimens and targeted therapies such as epidermal growth factor receptor therapy and have a better prognosis. Patients with right colorectal cancer do not respond well to conventional chemotherapies but demonstrate more promising results with immunotherapies because these tumors have a high antigenic load. It is essential for the development of effective therapeutic regimens and better treatment options to evaluate right- and left-sided tumors as separate entities and design the therapeutic regimen considering the differences between these two tumors. In the present review, we aimed to compare right and left colorectal cancers in terms of anatomical, histological, epidemiological, molecular and genetic perspectives and discuss the response of these tumors to adjuvant targeted therapy and immunotherapy.