
Cancer is a prototypical complex disease whose pathology cannot be properly understood by an individual player--gene, protein as well as molecular pathway, similar to that of a many-body phenomenon in physics. The rapidly accumulating large "omics" data in biological sciences provide more information on cancer but also requires a new mechanistic underpinning to integrate for rationalizing cancer complexity and to identify collective and individual roles of these players. A unifying and quantitative theory was proposed that cancer is a robust state, or a group of states, of the endogenous molecular-cellular network evolutionarily built for developmental processes and physiological functions. This state is not optimized for the whole organism. The crucial individual players for such a network were found, at least partially, which in turn suggests the existence of a hierarchical structure within biological systems. Such a structure enables a core network to be constructed from known experimental knowledge. By examining the nonlinear stochastic dynamics of the core network in the phase space, robust states corresponding to normal physiological and abnormal pathological phenotypes, including cancer, emerge naturally. The nonlinear dynamical model of the network leads to a more encompassing framework integrating existing biological knowledge than the currently prevailing linear-additive thinking in cancer research. So far, it has been applied to prostate, hepatocellular, leukemia, and gastric cancers. The quantitative models so constructed from individual molecular biology experiments recapitulate known clinical observations and predict new phenomena. This framework may serve as a platform of "dry experiments" for the search of new therapies on cancer. The endogenous molecular-cellular network theory may offer an example of carrying physics inquiring spirit far beyond: There must be general rules/laws to be discovered in biology and medicine. In my seminar I will present the basic considerations behind the approach and what has been achieved after more than 10 years of effort. The lecture is based on work done with Ruoshi Yuan, Xiaomei Zhu, Gaowei Wang, Site Li, Jerry Radich and Lee Hood.

Cancer is a prototypical complex disease whose pathology cannot be properly understood by an individual player--gene, protein as well as molecular pathway, similar to that of a many-body phenomenon in physics. The rapidly accumulating large "omics" data in biological sciences provide more information on cancer but also requires a new mechanistic underpinning to integrate for rationalizing cancer complexity and to identify collective and individual roles of these players. A unifying and quantitative theory was proposed that cancer is a robust state, or a group of states, of the endogenous molecular-cellular network evolutionarily built for developmental processes and physiological functions. This state is not optimized for the whole organism. The crucial individual players for such a network were found, at least partially, which in turn suggests the existence of a hierarchical structure within biological systems. Such a structure enables a core network to be constructed from known experimental knowledge. By examining the nonlinear stochastic dynamics of the core network in the phase space, robust states corresponding to normal physiological and abnormal pathological phenotypes, including cancer, emerge naturally. The nonlinear dynamical model of the network leads to a more encompassing framework integrating existing biological knowledge than the currently prevailing linear-additive thinking in cancer research. So far, it has been applied to prostate, hepatocellular, leukemia, and gastric cancers. The quantitative models so constructed from individual molecular biology experiments recapitulate known clinical observations and predict new phenomena. This framework may serve as a platform of "dry experiments" for the search of new therapies on cancer. The endogenous molecular-cellular network theory may offer an example of carrying physics inquiring spirit far beyond: There must be general rules/laws to be discovered in biology and medicine.

In my seminar I will present the basic considerations behind the approach and what has been achieved after more than 10 years of effort.

The lecture is based on work done with Ruoshi Yuan, Xiaomei Zhu, Gaowei Wang, Site Li, Jerry Radich and Lee Hood.