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Updated: May 19, 2026

High-throughput Identification of Synergistic Drug Combinations by the Overlap2 Method
Published on: May 21, 2018
Synergism between clofarabine and decitabine through p53R2: a pharmacodynamic drug-drug interaction modeling
Karen E Thudium1, Sampa Ghoshal, Gerald J Fetterly
1Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA.
Abstract:
Clofarabine (CLO), a purine nucleoside analog with promising efficacy in acute myeloid leukemia (AML), inhibits the ribonucleotidereductase, p53R2. We have shown that p53R2 mRNA is up-regulated by decitabine (DEC), another drug with promising activity in AML. We developed a pharmacodynamic model to characterize the interaction between CLO and DEC on an AML cell line and down-regulated p53R2 protein to understand its role. These results confirm a role for p53R2 in both CLO and DEC mechanism of action, demonstrate synergism between these two drugs in this AML model and support the use of this combination in a future clinical trial.
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