Cancer as a robust system: implications for anticancer therapy

Abstract

Cancers are extremely complex, heterogeneous diseases. Many approaches to anticancer treatment have had limited success — cures are still rare. A fundamental hurdle to cancer therapy is acquired tumour 'robustness'. The goal of this article is to present a perspective on cancer as a robust system to provide a framework from which the complexity of tumours can be approached to yield novel therapies.

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Figure 1: Feedback loops for hypoxia responses of tumour cells.
Figure 2: Simple computer simulations of robust and fragile cell cycles.
Figure 3: Complex interactions involving the p53 tumour suppressor.
Figure 4: Identification and manipulation of phase–space states in cellular dynamics.

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Acknowledgements

The author wishes to thank J. Doyle, M. Csete and T. Shiraishi for insightful discussions, anonymous reviewers for informative and constructive comments, and members of Sony Computer Science Laboratories, Inc. and the ERATO Kitano Symbiotic Systems Project for discussions. This research is, in part, supported by the Exploratory Research for Advanced Technology (ERATO) and Solution-Oriented Research for Science and Technology (SORST) programme (Japan Science and Technology Agency), the NEDO Grant (New Energy and Industrial Technology Development Organization (NEDO)/Japanese Ministry of Economy, Trade and Industry (METI)), the Special Coordination Funds for Promoting Science and Technology, the Center of Excellence Program for Keio University (Ministry of Education, Culture, Sports, Science, and Technology), the Rice Genome and Simulation Project (Japanese Ministry of Agriculture) and the Air Force Office of Scientific Research (AFOSR).

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ABL

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HIF1

MDM2

MDR1

MYC

p53

uPAR

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