A passage through systems biology to systems medicine: adoption of middle-out rational approaches towards the understanding of therapeutic outcomes in cancer.

During the last few decades, conventional practices in medicine including oncology focus their interests towards the reductionism of molecular detailing and at the analytical level population-based assessment with stochastic principles, technically called 'evidence-based medicine', is generally practiced. Due to fluctuations in physiological parameters, the analysis and prediction of a therapeutic outcome in cancer on an individual level is uncertain. In recent times the well accepted opinion is that cancer should be looked upon as a systems disorder. This makes a paradigm shift - from a fragmented to a systems approach, linear to nonlinear methodology and from genome to physiome based analysis to understand the cancer. In the arena of systems biology, different groups have different views, namely, bottom-up (mechanistic), top-down (operational) and middle-out (rational). With respect to cancer each has a special relevance to serve the specific objectivity. In this article we have reviewed the views of the different schools, recent developments and controversies associated with the uncertainties in prediction of the therapeutic outcome of cancer. Recent advances in dynamical science and control theory may provide suitable analytical tools for capturing the uncertainties associated with cancer therapy through the development of middle-out rationalist (MORA) views.