Cancer as robust intrinsic state of endogenous molecular-cellular network shaped by evolution

Abstract

An endogenous molecular--cellular network for both normal and abnormal functions is assumed to exist. This endogenous network forms a nonlinear stochastic dynamical system, with many stable attractors in its functional landscape. Normal or abnormal robust states can be decided by this network in a manner similar to the neural network. In this context cancer is hypothesized as one of its robust intrinsic states. This hypothesis implies that a nonlinear stochastic mathematical cancer model is constructible based on available experimental data and its quantitative prediction is directly testable. Within such model the genesis and progression of cancer may be viewed as stochastic transitions between different attractors. Thus it further suggests that progressions are not arbitrary. Other important issues on cancer, such as genetic vs epigenetics, double-edge effect, dormancy, are discussed in the light of present hypothesis. A different set of strategies for cancer prevention, cure, and care, is therefore suggested.

Figure 1

The minimum set of pathways and modules of the endogenous network. Endogenous molecular and cellular agents first form pathways and modules. Pathways and modules cross talk to each other to form the endogenous network.

Figure 2

Three typical situations of the functional landscape. The vertical scale illustrates the relative stability of robust states, healthy, tumor and others, in the multiple dimensional state space. a) The healthy state is a globally stable under normal conditions; b) Due to genetic and epidemiologic influence on the endogenous network, tumor or cancer states may become more stable than healthy state. Such metastable healthy state may still have a long life time for the whole organism being viable; c) A very “damaged” endogenous network may not be able to produce a locally stable healthy state.