title: A Perspective on Implementing a Quantitative Systems Pharmacology Platform for Drug Discovery and the Advancement of Personalized Medicine.
abstract: Drug candidates exhibiting well-defined pharmacokinetic and pharmacodynamic profiles that are otherwise safe often fail to demonstrate proof-of-concept in phase II and III trials. Innovation in drug discovery and development has been identified as a critical need for improving the efficiency of drug discovery, especially through collaborations between academia, government agencies, and industry. To address the innovation challenge, we describe a comprehensive, unbiased, integrated, and iterative quantitative systems pharmacology (QSP)-driven drug discovery and development strategy and platform that we have implemented at the University of Pittsburgh Drug Discovery Institute. Intrinsic to QSP is its integrated use of multiscale experimental and computational methods to identify mechanisms of disease progression and to test predicted therapeutic strategies likely to achieve clinical validation for appropriate subpopulations of patients. The QSP platform can address biological heterogeneity and anticipate the evolution of resistance mechanisms, which are major challenges for drug development. The implementation of this platform is dedicated to gaining an understanding of mechanism(s) of disease progression to enable the identification of novel therapeutic strategies as well as repurposing drugs. The QSP platform will help promote the paradigm shift from reactive population-based medicine to proactive personalized medicine by focusing on the patient as the starting and the end point.
authors.affiliation: Department of Computational and Systems Biology, Pittsburgh, PA, USA University of Pittsburgh Drug Discovery Institute, Pittsburgh, PA, USA.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Stern
authors.affiliation: Department of Computational and Systems Biology, Pittsburgh, PA, USA University of Pittsburgh Drug Discovery Institute, Pittsburgh, PA, USA The University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Schurdak
authors.affiliation: Department of Computational and Systems Biology, Pittsburgh, PA, USA University of Pittsburgh Drug Discovery Institute, Pittsburgh, PA, USA The University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
authors.forename: Ivet
authors.initials: I
authors.lastname: Bahar
authors.affiliation: Department of Computational and Systems Biology, Pittsburgh, PA, USA University of Pittsburgh Drug Discovery Institute, Pittsburgh, PA, USA University of Pittsburgh Institute for Personalized Medicine, Pittsburgh, PA, USA.
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Berg
authors.affiliation: Department of Computational and Systems Biology, Pittsburgh, PA, USA University of Pittsburgh Drug Discovery Institute, Pittsburgh, PA, USA The University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA dltaylor@pitt.edu.
authors.forename: D Lansing
authors.initials: DL
authors.lastname: Taylor
mesh_terms: D018450:Disease Progression; D015195:Drug Design; D055808:Drug Discovery; D004345:Drug Industry / Q000639:trends; D006801:Humans; D008954:Models, Biological; D057285:Precision Medicine
keywords: drug discovery; novel therapeutic strategies; personalized medicine; quantitative systems pharmacology