Efficacy of combined histone deacetylase and checkpoint kinase inhibition in a preclinical model of human Burkitt lymphoma

Yan Guo Kong, Gustavo Barisone, Ranjit S. Sidhu, Robert T O'Donnell, Joseph Tuscano

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Checkpoint kinase inhibition has been studied as a way of enhancing the effectiveness of DNA-damaging agents. More recently, histone deacetylase inhibitors have shown efficacy in several cancers, including non-Hodgkin lymphoma. To evaluate the effectiveness of this combination for the treatment of lymphoma, we examined the combination of AR42, a histone deacetylase inhibitor, and checkpoint kinase 2 (CHEK2) inhibitor II in vitro and in vivo. The combination resulted in up to 10-fold increase in potency in five Burkitt lymphoma cell lines when compared with either drug alone. Both drugs inhibited tumor progression in xenograft models, but the combination was more effective than either agent alone, resulting in regression of established tumors. No toxicity was observed. These results suggest that the combination of histone deacetylase inhibition and checkpoint kinase inhibition represent an effective and nontoxic treatment option that should be further explored in preclinical and clinical studies.

Original languageEnglish (US)
Pages (from-to)824-832
Number of pages9
JournalMolecular Medicine
Volume21
DOIs
StatePublished - Aug 24 2015

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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