Haniyeh Bashi zadeh Fakhar - Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Hakimeh Zali - School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical sciences,Tehran
Shabnam Jeibouei - School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical sciences,Tehran
Nazanin Ghasemi۲ - School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical sciences,Tehran

Aim & introduction;Cetuximab and panitumumab are EGF receptor (EGFR) inhibitors for patients with wild-type KRAS metastatic colorectal cancer. Acquired genetic and epigenetic mechanisms of resistance to EGFR therapy are considered in different clinical trials. In this study used the COSMIC database to reveal the resistance mechanisms of EGFR inhibitor in large intestinal patients who registered their information as drug resistance. Method: The COSMIC database contains different genomic and transcriptomics data from next-generation sequencing. We selected data from the patient with colorectal cancer who failed targeted therapy related to EGFR inhibitors. Results: Among 8828 patients, 222 patients were mutated samples (2.51%) in EGFR gene, among 771 samples, 15 samples gain Copy Number Variations (CNVs) (1.95%) in this receptor and from 610 samples, 61 samples (10%) overexpressed EGFR gene. In all sample study, the most common mutation was related to the EGFR p.T790M (c.x). Other essential genes were determined ABL1, MET, and NF2 that mutation connected to fail therapy. Conclusion:Results ascertained the correlation between CNV and overexpression of EGFR but are not allocated to all of the patients, because EGFR overexpression in some cases is not according to the raising CNVs. Besides mutation of EGFR lonely are not correspond to the drug resistance. It seems that the several genes and pathways progress resistance that their changes are different from the primary event in tumors because gene mutated are different from genes that their mutations before target therapy checked (including KRAS, NRAS, BRAF, PIK3CA, and EGFR). So target therapy modifies the profile of genomics in colorectal cancer patients ultimately develops drug resistant.

colorectal cancer, EGFR inhibitor, genomics, target therapy