***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Differences exist between the proximal and distal colon in terms of developmental origin , exposure to patterning genes , environmental mutagens , and gut flora . Little is known on how these differences may affect mechanisms of tumorigenesis , side-specific therapy response or prognosis . We explored systematic differences in pathway activation and their clinical implication s. MATERIAL S AND METHODS Detailed clinicopathological data for 3045 colon carcinoma patients enrolled in the PETACC3 adjuvant chemotherapy trial were available for analysis . A subset of 1404 sample s had molecular data , including gene expression and DNA copy number profiles for 589 and 199 sample s , respectively . In addition , 413 colon adenocarcinoma from TCGA collection were also analyzed .  Tumor side-effect on anti-epidermal growth factor receptor ( EGFR ) therapy  was assessed in a cohort of 325 metastatic patients . Outcome variables considered were relapse-free survival and survival after relapse ( SAR ) . RESULTS Proximal carcinomas were more often mucinous , microsatellite instable (MSI)-high , mutated in key tumorigenic pathways , expressed a B-Raf proto-oncogene , serine/threonine kinase (BRAF)-like and a serrated pathway signature , regardless of histological type . Distal carcinomas were more often chromosome instable and EGFR or human epidermal growth factor receptor 2 ( HER2 ) amplified , and more frequently overexpressed epiregulin . While risk of relapse was not different per side , SAR was much poorer for proximal than for distal stage III carcinomas in a multivariable model including BRAF mutation status [ N = 285 ; HR 1.95 , 95 % CI ( 1.6 - 2.4 ) , P < 0.001 ] . Only patients with metastases from a distal carcinoma responded to anti-EGFR therapy , in line with the predictions of our pathway enrichment analysis . CONCLUSIONS Colorectal carcinoma side is associated with differences in key molecular features , some immediately druggable , with important prognostic effects which are maintained in metastatic lesions . Although within side significant molecular heterogeneity remains , our findings justify stratification of patients by side for retrospective and prospect i ve analyses of drug efficacy and prognosis 
    Output:
    
Conclusions Anti-EGFR mAbs have advantages in the tumor shrinkage regardless of left- or right-sided tumors , which is important for conversion therapy .
For right-sided tumors , anti-EGFR mAbs should remain the first choice for potentially curative resection in RAS wild-type mCRC patients .
ETS may represent a subgroup of patients with right-sided tumors who might benefit from the anti-EGFR mAb