Eyes on systems pharmacology.

As an emerging subdiscipline of pharmacology, one of the priary goals of systems pharmacology is to elucidate therapeutic echanisms of combined pharmacological strategies used to treat iverse complex diseases in which multiple integrated cellular athways are perturbed. Mechanistic insights into disease pathogenesis are critical for ptimal therapeutic development. With the exception of rare onoor oligogenic disorders caused by clearly defined mutaion(s), most common disorders such as neurological and heart iseases are caused by a combination of genetic, environmental, nd unidentified factors making them highly complex in nature 1]. In addition to the multifactorial etiology that remains to be lluminated for most complex disorders, the molecular changes ssociated with a given disease state are increasingly recognized to e dynamic and multi-faceted. Crosstalk between multiple signalng and metabolic pathways is often initiated, and network changes ccur as the disease progresses. In addition to perturbations in ntracellular processes, changes in cell-cell interaction networks, hich are extremely complicated even under normal physiologial conditions, add another layer of complexity to delineating the tiology of a disease and ascertaining the most effective therapeutic pproach [2]. Such intricacies generally necessitate multi-faceted reatment strategies. Drug combinations that therapeutically modlate different mechanistic nodes within a network may enable etter outcomes than single drug treatments [3]. Developing a novel drug is notoriously time-consuming and equires enormous financial investment as well as large-scale esearch efforts. Thus, reducing the time and cost as well as improvng success rates are of strategic importance in drug development. ne practical avenue to achieve this goal is drug repurposing; a rocess which identifies novel applications for approved pharmaological agents. Advances in “omics” have demonstrated that diseases often re better described not by symptoms or a single endpoint, but y the molecular environment of the whole cell, tissue or organsm. Systems pharmacology identifies therapies or combinations of herapies that best normalize a perturbed cellular or tissue milieu with minimal side effects) based on the breadth of molecular bnormalities associated with a particular disease. Thus, systems harmacology could facilitate the development of new therapies ased on existing drugs by seamlessly incorporating mechanistic ndings of a given disease with known pharmacological profiles of rugs.