The Yin-Yang Dynamics in Cancer Pharmacogenomics and Personalized Medicine.

The enormous heterogeneity of cancer systems has made it very challenging to overcome drug resistance and adverse reactions to achieve personalized therapies. Recent developments in systems biology, especially the perception of cancer as the complex adaptive system (CAS), may help meet the challenges by deciphering the interactions at various levels from the molecular, cellular, tissue-organ, to the whole organism. The ubiquitous Yin-Yang interactions among the coevolving components, including the genes and proteins, decide their spatiotemporal features at various stages from cancer initiation to metastasis. The Yin-Yang imbalances across different systems levels, from genetic mutations to tumor cells adaptation, have been related to the intra- and inter-tumoral heterogeneity in the micro- and macro-environments. At the molecular and cellular levels, dysfunctional Yin-Yang dynamics in the cytokine networks, mitochondrial activities, redox systems, apoptosis, and metabolism can contribute to tumor cell growth and escape of immune surveillance. Up to the organism and system levels, the Yin-Yang imbalances in the cancer microenvironments can lead to different phenotypes from breast cancer to leukemia. These factors may be considered the systems-based biomarkers and treatment targets. The features of adaptation and nonlinearity in Yin-Yang dynamical interactions should be addressed by individualized drug combinations, dosages, intensities, timing, and frequencies at different cancer stages. The comprehensive "Yin-Yang dynamics" framework would enable powerful approaches for personalized and systems medicine strategies.