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Full-Text Articles in Biochemistry, Biophysics, and Structural Biology
Differential Activity Of The Kras Oncogene By Method Of Activation: Implications For Signaling And Therapeutic Intervention, Nathan Ihle
Dissertations & Theses (Open Access)
Despite having been identified over thirty years ago and definitively established as having a critical role in driving tumor growth and predicting for resistance to therapy, the KRAS oncogene remains a target in cancer for which there is no effective treatment. KRas is activated b y mutations at a few sites, primarily amino acid substitutions at codon 12 which promote a constitutively active state. I have found that different amino acid substitutions at codon 12 can activate different KRas downstream signaling pathways, determine clonogenic growth potential and determine patient response to molecularly targeted therapies. Computer modeling of the KRas structure …