Network analysis of oncogenic Ras activation in cancer |
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Authors: | Stites Edward C Trampont Paul C Ma Zhong Ravichandran Kodi S |
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Institution: | Beirne B. Carter Center for Immunology Research and the Department of Microbiology, University of Virginia, Charlottesville, VA 22908, USA. |
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Abstract: | To investigate the unregulated Ras activation associated with cancer, we developed and validated a mathematical model of Ras signaling. The model-based predictions and associated experiments help explain why only one of two classes of activating Ras point mutations with in vitro transformation potential is commonly found in cancers. Model-based analysis of these mutants uncovered a systems-level process that contributes to total Ras activation in cells. This predicted behavior was supported by experimental observations. We also used the model to identify a strategy in which a drug could cause stronger inhibition on the cancerous Ras network than on the wild-type network. This system-level analysis of the oncogenic Ras network provides new insights and potential therapeutic strategies. |
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