Perspective abstract
Nature Chemical Biology 2, 458 - 466 (2006)
Published online: 18 August 2006 | doi:10.1038/nchembio817
Systems biology and combination therapy in the quest for clinical efficacy
Jonathan B Fitzgerald1, Birgit Schoeberl1, Ulrik B Nielsen1 & Peter K Sorger2
Abstract
Combinatorial control of biological processes, in which redundancy and multifunctionality are the norm, fundamentally limits the therapeutic index that can be achieved by even the most potent and highly selective drugs. Thus, it will almost certainly be necessary to use new 'targeted' pharmaceuticals in combinations. Multicomponent drugs are standard in cytotoxic chemotherapy, but their development has required arduous empirical testing. However, experimentally validated numerical models should greatly aid in the formulation of new combination therapies, particularly those tailored to the needs of specific patients. This perspective focuses on opportunities and challenges inherent in the application of mathematical modeling and systems approaches to pharmacology, specifically with respect to the idea of achieving combinatorial selectivity through use of multicomponent drugs.
- Jonathan B. Fitzgerald, Birgit Schoeberl and Ulrik B. Nielsen are at Merrimack Pharmaceuticals, One Kendall Square, Building 700 2nd floor, Cambridge, Massachusetts 02139, USA.
- Peter K. Sorger is at the Center for Cell Decision Processes, Departments of Biology and Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA, and the Department of Systems Biology, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA.
Correspondence to: Peter K Sorger2 e-mail: psorger@mit.edu
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