Journal
STATISTICS IN MEDICINE
Volume 33, Issue 24, Pages 4227-4236Publisher
WILEY-BLACKWELL
DOI: 10.1002/sim.6229
Keywords
drug combination; drug interaction; factorial design; Hill model; response surface model
Categories
Funding
- NSF DMS [1106854]
- NIH CA [091791]
- Division Of Mathematical Sciences
- Direct For Mathematical & Physical Scien [1106854] Funding Source: National Science Foundation
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Combination chemotherapy with multiple drugs has been widely applied to cancer treatment owing to enhanced efficacy and reduced drug resistance. For drug combination experiment analysis, response surface modeling has been commonly adopted. In this paper, we introduce a Hill-based global response surface model and provide an application of the model to a 512-run drug combination experiment with three chemicals, namely AG490, U0126, and indirubin-3'-monoxime (I-3-M), on lung cancer cells. The results demonstrate generally improved goodness of fit of our model from the traditional polynomial model, as well as the original Hill model on the basis of fixedratio drug combinations. We identify different dose-effect patterns between normal and cancer cells on the basis of our model, which indicates the potential effectiveness of the drug combination in cancer treatment. Meanwhile, drug interactions are analyzed both qualitatively and quantitatively. The distinct interaction patterns between U0126 and I-3-M on two types of cells uncovered by the model could be a further indicator of the efficacy of the drug combination. Copyright (c) 2014 John Wiley & Sons, Ltd.
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