Synergism between clofarabine and decitabine through p53R2: A pharmacodynamic drug-drug interaction modeling

Karen E. Thudium, Sampa Ghoshal, Gerald J. Fetterly, Jason P.Den Haese, Adam R. Karpf, Meir Wetzler

Research output: Contribution to journalArticle

4 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1410-1416
Number of pages7
JournalLeukemia Research
Volume36
Issue number11
DOIs
StatePublished - Nov 1 2012

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Keywords

  • AML
  • Clofarabine
  • Decitabine
  • Pharmacodynamic modeling
  • Synergy

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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