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Network Analysis of Oncogenic Ras Activation in Cancer

Science, 19 October 2007
Vol. 318, Issue 5849, p. 463-467
DOI: 10.1126/science.1144642

Network Analysis of Oncogenic Ras Activation in Cancer

  1. Edward C. Stites1,2,3,
  2. Paul C. Trampont1,
  3. Zhong Ma1,
  4. Kodi S. Ravichandran1,*
  1. 1 Beirne B. Carter Center for Immunology Research and the Department of Microbiology, University of Virginia, Charlottesville, VA 22908, USA.
  2. 2 Medical Scientist Training Program, University of Virginia, Charlottesville, VA 22908, USA.
  3. 3 Interdisciplinary Program of Biophysics, University of Virginia, Charlottesville, VA 22908, USA.
  1. * To whom correspondence should be addressed. E-mail: Ravi{at}virginia.edu

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.

  • Received for publication 4 May 2007.
  • Accepted for publication 6 September 2007.

Citation:

E. C. Stites, P. C. Trampont, Z. Ma, and K. S. Ravichandran, Network Analysis of Oncogenic Ras Activation in Cancer. Science 318, 463-467 (2007).

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