Right sided colon cancers include those of the cecum, descending colon, in the proximal 2/3 of the transverse colon.
The right sided colon cancers arise embryo logically from the midgut.
Left-sided tumors comprise those of the distal 1/3 of the transverse colon, descending colon, the sigmoid colon, and the rectum, and arise from the hind gut embryo logically.
Right sided and left sided cancers are commonly defined as proximal and distal to the splenic flexure, respectively.
The left and right sides of the colon or supported by the inferior and superior mesenteric arteries, respectively.
Left-sided and right-sided colorectal cancers differ extensively in terms of gene expression, DNA mutations, and methylation profile.
The colon proximal and distal it to the splenic flexure it may be considered as two distinct organs: differing in embryonic origin, arterial supply, bacterial flora, luminal content, along with biological and clinical pathologic differences.
Left-sided and right sided CRCs different epidemiologic trends in outcomes.
Patients with left sided: tumors tend to have superior overall survival compared with patients with right sided tumors.
Right sided primary tumors are associated with advanced presentation, BRAF,RAS PI3KCA mutations, large Chromosome alterations, deficient mismatch repair status and tendency to metastasize to the peritoneum.
Approximately 2/3 of sporadic colon cancers are left-sided and harbor traditional alterations, whereas one third are right sided and follow different carcinogenic pathways.
Patients with right sided: tumors are more poorly differentiated and have a higher rate of KRAS mutations than left-sided tumors.
Individuals with the driver germline genetic alterations of hereditary syndrome show a propensity to the development of right-sided tumors.
The primary tumor site is correlated with survival in the stage dependent fashion and responses to targeted therapy in patients with metastatic disease.
CRC represents a biological continuing rather than a dichotomy define by anatomical or embryonic landmarks.
Left-sided and right sided CRC’s exhibit unique genetic, epigenetic, transcriptional, and proteonomic levels, as well as differences within the microbiome.
Rectal cancer is a frequently include with left sided cooler cancers for purposes of sightedness analyses.
Differences in gut microbiome, related to increased bile acid exposure on the right side and predominate bacteria on the two sides of the colon may play a role in the phenotype of colorectal sightedness.
At least 1300 genes have been identified with distinct expression patterns in left-sided and right-sided CRC’s.
Right-sided tumors display a hypermutated genotype that is largely diploid and in which MSI is relatively prevalent, whereas left-sided tumors more frequently show loss of heterozygosity and chromosomal instability.
Left-sided tumors or clinically in Ridgewood KRAS mutations, EGF 4/EGR to amplification‘s, and a high level of amphiregulin and epiregulin expression.
Right-sided tumors are rich for RAF, PI3KCA, and TGFBR 2 mutations.
There is a difference in DNA methylation between left-sided and right sided colorectal cancers.
Right-Sided CRC‘s are characterized by adverse prognostic factors, including a serrated pathway signature and mucinous , undifferentiated histology.
Differences in the microbiome have been demonstrated with Fusobacterium, as Escherichia-shigella Leptotrichia more abundant and left-sided tumors, and Prevotella, Peptostreptococcus, and Selenomonas more prevalent in right sided tumors.
EGFR antibody agents such as cetuximab and panitumumab should only be used in RAS and BRAF wild-type left-sided CRC.
Right-sided compared with left-sided colorectal tumors were found to have higher BRAF Mutation frequency and more likely to be MSI-high (MSI-H).
While type RAS cancers are far more likely to derive benefit from EGFR inhibition if their cancers are left-sided rather than right sided.
In stage III: cancer, the favorable prognostic benefit of deficient mismatch repair status is restricted to patient who have right-sided tumors: patients who have left-sided deficient mismatch repair tumors have worse prognosis in regard to disease-free survival and overall survival in patients than with right sided deficient mismatch repair cancers.
KRAS mutation is associated with a poor overall survival in left-sided than in right sided colon cancer, among patients with stage III disease.
For patients with KRAS WT tumors only, those with left-sided tumors have any increased progression free survival benefit from cetuximab compared with supportive care, whereas those with right sided tumors received no benefit.
Studies have shown a response to chemotherapy plus anti-EGFR therapy in patients with left-sided BRAF/RAS WT tumors, while those on the right sided tumors had adverse outcomes to anti-EGFR therapy but benefited from chemotherapy plus VEGF intervention.
Patients with wild type RAS cancers are far more likely to derive benefit from EGFR inhibition if their cancers are left-sided rather than right sided.
In five randomized first line trials the predictive effective tumor side on outcomes in patients with cetuximab or panitumumab in combination with chemotherapy: only patients with left-sided tumors had a significant improvement in progression free survival.
Proximal tumors more often present it later stages and are associated with worse overall survivals relative to distal cancers.
Left-sided and right sided colorectal tumors are increasingly recognizes unique cancers that respond to different therapeutic strategies.
Metastatic colorectal cancer patients have longer overall survival, longer progression free survival, and lower mortality rates if the tumors are left-sided rather than right sided.
In a meta-analysis of 398,687 patients in five studies there was no significant difference in five-year overall survival between patients with right sided colon cancer in those with left-sided colon cancer after curative resection (Ishizuka M).