Systems engineering meets Quantitative Systems Pharmacology: From low-level targets to engaging the host defenses

Quantitative systems pharmacology aims at systematizing, in a model-based manner, the integration of systems biology and pharmacology in an effort to rationalize the process of assessing the ability of a drug to enhance well-being off-setting the effects of a disease. Systems engineering, on the other hand, has enabled us to develop principles and methodologies for designing and operating engineered networks of structures exploring the integration of the underlying governing (design) laws. Although the computational tools, which have resulted in major advances in the design, analysis, and operation of complex engineered structures, have had tremendous success in the analysis of systems pharmacology models, we will argue in this presentation, that exploring the underlying conceptual foundation of complex systems engineering will enable us to move towards integrated models at the host level to explore, and possibly, induce synergies between low-level drug targets and engaging higher level, systemic, defence mechanisms. This is an approach which would require refocusing of the key activities; however, it is likely the more promising approach as we enter the new era of personalized and precision medicine. We finally argue for the development of an allostatic approach to quantitative systems pharmacology and the development of an integrated framework for considering drugs in their broader context, beyond their local site of action.