Mutation Studies of KRAS Proto oncogene and In Silico Drug Designing against Non-Small Cell Lung Cancer
Abstract
Based upon the microscopic appearance of the tumor cells, Lung cancers, also known as bronchogenic carcinomas, are broadly classified into two types: small cell lung cancers (SCLC) and non-small cell lung cancers (NSCLC). Lung cancer is the significant contributor of increased cancer deaths. It is evident that the pathway of lung cancer includes both RAS-mediated and non-RAS-mediated mechanisms. Cancer is initiated by activation of oncogenes or inactivation of tumor suppressor genes. Mutations in the K-ras proto-oncogene are responsible for 10–30% of adenocarcinomas. Many of the mutations of KRAS have been reported worldwide to be involved in Non small cell Lung cancer. The current study involves checking the occurrence of one of these SNPs (rs104894361) in the target population. The work is further extended by investigating the role of natural antioxidants in inhibiting the mutated KRAS thereby reducing the cell proliferation rate. The work involves collection of Blood samples from various lung cancer patients along with their case history and medication details. The blood sample is processed further for DNA isolation, KRAS gene amplification and sequencing. While grouping the samples for processing, emphasis was given on their smoking status and it was concluded that smoking increases the possibility of target SNP hence leading to NSCLC. Further in in silico work a comprehensive analysis of KRAS at genomic and Proteomic level was conducted and docking studies were performed on mutated KRAS with screened Antioxidants. A comparative assessment of the docking energies revealed that many antioxidants like 2-Cys peroxiredoxin BAS1, Ascorbate peroxidase, Lectin and Lactoferrin have a better docking interaction with mutated KRAS than Trimetrixate, the conventional drug against NSCLC.
References
3. Koji Okudela, Tetsukan Woo, Hitoshi Kitamura. KRAS gene mutations in lung cancer: Particulars established and issues unresolved: Article first published online: 12 JUL 2010,DOI: 10.1111/j.1440-1827.2010.02580.
4. Li M, Liu L, Liu Z, Yue S, Zhou L, Zhang Q, Cheng S, Li RW, Smith PN, Lu S.The status of KRAS mutations in patients with non-small cell lung cancers from mainland China: Oncol Rep. 2009 Nov; 22(5):1013-20. 5. McKeage, Mark J., et al. Phase II Study of ASA404 (vadimezan, 5,6-dimethylxanthenone-4-acetic acid/DMXAA) 1800 mg/m2 Combined With Carboplatin and Paclitaxel in Previously Untreated Advanced Non-Small Cell Lung Cancer. Lung Cancer 65.2 Aug.
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