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Network analysis of oncogenic Ras activation in cancer.

by: E. C. Stites, P. C. Trampont, Z. Ma, K. S. Ravichandran
Science (New York, N.Y.), Vol. 318, No. 5849. (19 October 2007), pp. 463-467.

X 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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This article has been bookmarked 7 times, initially on 2007-10-21.

2009-07-02 User mingzhi
2009-06-17 Group Complex Networks
User fesousa
2007-11-23 User oelemento , 1 note

This fascinating paper describes a mathematical model of Ras signaling. The model is able to predict why certain mutations (Ras G12V) are more often found in cancer than others (Ras F28L): because they increase the output of the Ras pathway in vivo by a larger amount.

The same model predicts therapeutically beneficial strategies, that would target diseased cells (with Ras activating mutations) and not normal cells: a hypothetical drug that would sequester Ras-GTP would reduce Ras output by a larger amount in the cancerous Ras pathway compared to WT pathway.

2007-11-23 23:14:20
2007-11-09 User jackjackjjj
2007-10-24 User zwang
2007-10-21 User shigepong
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