Difference Between Left-Sided and Right-Sided Colorectal Cancer: A Focused Review of Literature

Abstract

Colorectal cancer is the third most common cancer worldwide with a high mortality rate at the advanced stages. However, colorectal cancer is not a single type of tumor; its pathogenesis depends on the anatomical location of the tumor and differs between right side and left side of the colon. Tumors in the proximal colon (right side) and distal colon (left side) exhibit different molecular characteristics and histology. In the right-sided tumors, mutations in the DNA mismatch repair pathway are commonly observed; and these tumors generally have a flat histology. In the left-sided tumors, chromosomal instability pathway-related mutations, such as KRAS, APC, PIK3CA, p53 mutations are observed and these tumors demonstrate polypoid-like morphology. Therapy responses are totally different between these tumor entities. Left-sided colorectal cancer (LCRC) patients benefit more from adjuvant chemotherapies such as 5-fluorouracil (5-FU)-based regimes, and targeted therapies such as anti- epidermal growth factor receptor (EGFR) therapy, and have a better prognosis. Right-sided colorectal cancer (RCRC) patients do not respond well to conventional chemotherapies, but demonstrate more promising results with immunotherapies because these tumors have high antigenic load. For the development of effective therapy regimes and better treatment options, it is essential to evaluate right-sided and left-sided tumors as separate entities, and design the therapy regime considering the differences between these tumors.

The Prognostic Value of the Detection of Microbial Translocation in the Blood of Colorectal Cancer Patients

“…It was observed that patients with right-sided tumors presented a significantly decreased OS compared to left-sided tumors. This phenomenon has also been described previously [39][40][41][42]. Baran B et al reported that treatment response differed among the left and right-sided tumors.…”

Guardant360 Circulating Tumor DNA Assay Is Concordant with FoundationOne Next-Generation Sequencing in Detecting Actionable Driver Mutations in Anti-EGFR Naive Metastatic Colorectal Cancer

“…We found that the majority of patients who had more than four gene amplifications had left‐sided colon cancer. This is consistent with prior studies that have shown that left‐sided colon cancers tend to have an increased chromosomal instability high tumor (CIN high) compared with right‐sided tumors . CIN high tumors are characterized by widespread imbalances in chromosome number and loss of heterozygosity and, hence, may have increased copy number variations in those tumors .…”

Degree and site of chromosomal instability define its oncogenic potential

“…It is therefore intriguing that addition of moderate to high CIN to this model causes early occurrence of colon adenomas, thus making it a better model for human disease. Furthermore, as in human FAP, colonic adenomas of CiMKi;Apc Min/+ mice are predominantly located in the distal colon and are aneuploid and karyotypically heterogeneous 71 . Also, in contrast to adenomas from Apc Min/+ mice 58 , LOH in CiMKi;Apc Min/+ mice did not occur by loss of (part of) the wild-type allele.…”