Science. 2007 Oct 19;318(5849):463-7.

Network analysis of oncogenic Ras activation in cancer.

Stites EC, Trampont PC, Ma Z, Ravichandran KS.

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Beirne B. Carter Center for Immunology Research and the Department of Microbiology, University of Virginia, Charlottesville, VA 22908, USA.

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.

PMID:: 17947584; [PubMed - indexed for MEDLINE]

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Network analysis of oncogenic Ras activation in cancer.

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