Yang, R., Niepel, M., Mitchison, T.K., and Sorger, P.K. (2010). Dissecting Variability in Responses to Cancer Chemotherapy through Systems Pharmacology. Clin Pharmacol Ther 88, 34-38. PMC2941986.
Abstract
Variability in patient responses to even the most potent and targeted therapeutics is now the primary challenge facing drug discovery and patient care, particularly in oncology and immune therapy. Variability with respect to mechanisms of induced resistance is observed both in drug-naive patients and among those who are initially responsive. Genomics has developed powerful tools for systematic interrogation of disease genotype and transcriptional states (particularly in cancer) and for correlation of these measures with parameters of disease such as histological diagnosis and outcome. In contrast, mechanistic preclinical studies remain relatively narrowly focused, leading to many apparent contradictions and poor understanding of the determinants of response. We describe the emergence of a systems pharmacology approach that is mechanistic, quantitative, probabilistic, and postgenomic and promises to do for mechanistic pharmacology what genomics is doing for correlative studies. We focus on studies in cell lines (which currently dominate mechanism-oriented analysis), but our arguments are equally valid for real tumors studied in short-term culture as xenografts and, perhaps some time in the future, in humans.
Very interesting the merging of the two areas of research, I hope it successfully moves forward.
I wonder if the following would be an interesting poster subject for an upcoming, related conference:
The Role of Systems Pharmacology in the Realm of an Orphan Disease Like Waldenstrom’s Macroglobulinemia