Abstract
There are 3 types of RAS oncogene, K RAS, N RAS, H RAS. This RAS can be diagnosed through Real Time PCR. H RAS point mutation is responsible for bladder cancer whereas N RAS point mutation is responsible for Hematopoietic tumors. K RAS point mutation is most important and it cause NON SMALL CELL LUNG CANCER, Carcinoma of Colon, Carcinoma of pancreas. K RAS is the molecular on/off switch. When turned on, it recruits and activates proteins necessary for the proliferation of growth factor and their receptors’ signal such as c-Raf and PI 3-kinase. In Combination with GTP, KRAS possesses an intrinsic enzymatic activity which cleaves the terminal phosphate of the nucleotide, and finally make itself turn off. For over 30 years, the protein KRAS is a major challenge in drug design. So far, there is no approved therapy for patients with KRAS mutations, which comprise around 25% of patients with lung cancer. Achilles heel small molecules in K RAS G12C, subverting the native nucleotide preference to favour GDP over GTP and impairing binding to Raf. Dr. Nathanael S. Gray, in the Department of Cancer Biology at the Dana-Farber Cancer Institute, reported the synthesis of a GDP analogue(SML-8-73-1) and a prodrug derivative (SML-10-70-1), which were selective, direct-acting covalent inhibitors of the KRAS (G12C) mutant relative to wild-type Ras. An orally available agent that targets the specific KRAS mutation, p.G12C, with potential anti-neoplastic activity. Upon oral administration, KRAS mutant-targeting AMG 510 selectively targets the KRAS p.G12C mutant, at either the DNA, RNA or protein level, and prevents, through an as of yet not elucidated manner, expression of and/or tumor cell signaling through the KRAS p.G12C mutant. This may inhibit growth in KRAS p.G12C-expressing tumor cells. The KRAS p.G12C mutation is seen in some tumor cell types and plays a key role in tumor cell proliferation.
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