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From Phage lambda to human cancer: endogenous molecular-cellular network hypothesis

Authors
  • Wang, Gaowei1, 2
  • Zhu, Xiaomei3
  • Hood, Leroy4
  • Ao, Ping1, 2, 5
  • 1 Shanghai Jiao Tong University, Ministry of Education Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai, 200240, China , Shanghai (China)
  • 2 Shanghai Jiao Tong University School of Medicine, State Key Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai, 200032, China , Shanghai (China)
  • 3 GenMath, Corp., Seattle, WA, 98105, USA , Seattle (United States)
  • 4 Institute for Systems Biology, Seattle, WA, 98103, USA , Seattle (United States)
  • 5 Shanghai Jiao Tong University, Department of Physics, Shanghai, 200240, China , Shanghai (China)
Type
Published Article
Journal
Quantitative Biology
Publisher
Springer-Verlag
Publication Date
Feb 06, 2013
Volume
1
Issue
1
Pages
32–49
Identifiers
DOI: 10.1007/s40484-013-0007-1
Source
Springer Nature
Keywords
License
Yellow

Abstract

Experimental evidences and theoretical analyses have amply suggested that in cancer genesis and progression genetic information is very important but not the whole. Nevertheless, “cancer as a disease of the genome” is still currently the dominant doctrine. With such a background and based on the fundamental properties of biological systems, a new endogenous molecular-cellular network theory for cancer was recently proposed by us. Similar proposals were also made by others. The new theory attempts to incorporate both genetic and environmental effects into one single framework, with the possibility to give a quantitative and dynamical description. It is asserted that the complex regulatory machinery behind biological processes may be modeled by a nonlinear stochastic dynamical system similar to a noise perturbed Morse-Smale system. Both qualitative and quantitative descriptions may be obtained. The dynamical variables are specified by a set of endogenous molecular-cellular agents and the structure of the dynamical system by the interactions among those biological agents. Here we review this theory from a pedagogical angle which emphasizes the role of modularization, hierarchy and autonomous regulation. We discuss how the core set of assumptions is exemplified in detail in one of the simple, important and well studied model organisms, Phage lambda. With this concrete and quantitative example in hand, we show that the application of the hypothesized theory in human cancer, such as hepatocellular carcinoma (HCC), is plausible, and that it may provide a set of new insights on understanding cancer genesis and progression, and on strategies for cancer prevention, cure, and care.

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