Systems biology and combination therapy in the quest for clinical efficacy

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' phar...

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Bibliographic Details
Published inNature chemical biology Vol. 2; no. 9; pp. 458 - 466
Main Authors Sorger, Peter K, Fitzgerald, Jonathan B, Schoeberl, Birgit, Nielsen, Ulrik B
Format Journal Article
LanguageEnglish
Published United States Nature Publishing Group 01.09.2006
Subjects
Biology
Disease
Drug dosages
Drug Therapy, Combination
Feedback, Physiological
Kinases
Mathematical models
Models, Biological
Pharmaceuticals
Pharmacology
Physiology
Proteins
Systems Biology
Toxicity
United States > US
Massachusetts
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Summary: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.
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ISSN:1552-4450
1552-4469
DOI:10.1038/nchembio817