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Science 318 (5849): 463-467

Copyright © 2007 by the American Association for the Advancement of Science

Network Analysis of Oncogenic Ras Activation in Cancer

Edward C. Stites,1,2,3 Paul C. Trampont,1 Zhong Ma,1 Kodi S. Ravichandran1*

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.

1 Beirne B. Carter Center for Immunology Research and the Department of Microbiology, University of Virginia, Charlottesville, VA 22908, USA.
2 Medical Scientist Training Program, University of Virginia, Charlottesville, VA 22908, USA.
3 Interdisciplinary Program of Biophysics, University of Virginia, Charlottesville, VA 22908, USA.

* To whom correspondence should be addressed. E-mail: Ravi{at}virginia.edu


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