KRAS mutations as marker for resistance detection against anti-EGFR therapy in colorectal cancer Patients

KRAS proto-oncogene is a small signaling Switch molecule with GTPase Activity, and the specific mutations on the gene lead to increment of cytoplasmic of RAS-GTP. Oncogenic signaling pathways, such as Raf-MEK-ERK and PI3K/AKT cascades, are then constitutively activated in an EGFR activation-independent manner and therefore promote cell cycle progression. Using anti-EGFR monoclonal antibodies (mAbs) such as cetuximab and panitumumab, led to inhibition of EGFR activity, But mAbs can t be switching off downstream pathways in patients with KRAS mutations. The purpose of this study is introduction of hot spots KRAS mutations and role of these mutations on selecting a useful therapeutic strategy. This study was performed on 52 patients having colorectal cancer who referred to the AL-Zahra hospital in Isfahan. The total DNA was extracted from fresh tumor and normal tissues. Exon 2 of KRAS gene was amplified and sequenced for detection the mutation points. The mutations were analyzed, and correlations with clinicopathological features were assessed. In this study, the prevalence of KRAS gene mutations was 15/4% (8 out of 52 cases). The two G12D and G12A types of mutations and the only G13D type of mutation were found in codon 12(75%) and codon 13(25%), respectively. Common tumor sites were rectum and rectosigmoid. The mean ages for patients were 61/2 years (range: 31-87 years). There was no significant relationship between the mutation and clinical and pathological aspects of the disease (p 0.05). Molecular examinations for detection and screening of KRAS gene mutations in patients with metastatic colorectal carcinoma cause to saving time and expense, and help to select a suitable treatment pathway.