Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 113, Issue 37, Pages 10442-10447Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1606301113
Keywords
drug combinations; drug cocktails; cancer treatment; mechanism-free formula; predictive formula
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Funding
- Clore-Katz-David Foundation
- Fela Shapell Family Foundation
- Israel National Center for Personalized Medicine (INCPM)
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Finding potent multidrug combinations against cancer and infections is a pressing therapeutic challenge; however, screening all combinations is difficult because the number of experiments grows exponentially with the number of drugs and doses. To address this, we present a mathematical model that predicts the effects of three or more antibiotics or anticancer drugs at all doses based only on measurements of drug pairs at a few doses, without need for mechanistic information. The model provides accurate predictions on available data for antibiotic combinations, and on experiments presented here on the response matrix of three cancer drugs at eight doses per drug. This approach offers a way to search for effective multidrug combinations using a small number of experiments.
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