Systems Pharmacology in Cancer
This chapter focuses on systems approach that can be successfully applied to the processes aimed at developing better anticancer therapeutic agents. Given the complexity of the human disease and the robust phenotypes of biological systems, it seems unlikely that modulating a single protein will be able to effectively reverse the disease process for every patient. This is particularly true in cancer, as the malignant process involves several aberrant compensatory signaling routes that bypass the inhibition of individual proteins. However, the major advance has been acquisition of the ability for precise measurement of the fundamental units of a complex system in a multiplex fashion, and thereby the ability to measure and to quantify the complexity. Accurate models of such systems provide the potential for predicting cellular outcomes. Systems strategies in cancer pharmacology can therefore be used to direct experimental focus, identify new targets for specific disease states, uncover mechanisms of action of a compound, identify likely combination therapies, and generate biomarkers of response. With the knowledge of the genome sequences, genetic tools to interrupt the function of specific genes and the availability of large libraries of small molecules targeting specific protein products, such systems approaches are now productive. Although the future is bright, applications of systems approaches in cancer pharmacology remain nascent and incomplete. There are special characteristics of cancer that both challenge and accelerate discovery in this field. The greatest challenge is the genetic plasticity and resulting complexity of the cancer genome; because of the unique mutations, rearrangements, and epigenetic changes, every cancer is a special genome in itself.