Poly (ADP-ribose) polymerase inhibitor LT-626: Sensitivity correlates withMRE11mutations and synergizes with platinums and irinotecan in colorectal cancer cells

Some colorectal cancers (CRC) display microsatellite instability (MSI) leading to mutations in genes such asMRE11. The aim of this study was to determine whether MSI orMRE11mutational status correlates with sensitivity to the PARP inhibitor LT-626 and whether LT-626 synergizes with DNA-damaging chem...

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Bibliographic Details
Published inCancer letters Vol. 343; no. 2; p. 217
Main Authors McPherson, Lisa A, Shen, Yuqiao, d, James M
Format Journal Article
LanguageEnglish
Published Clare Elsevier Limited 28.02.2014
Subjects
Colorectal cancer
DNA repair
Mutation
Rodents
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Summary:Some colorectal cancers (CRC) display microsatellite instability (MSI) leading to mutations in genes such asMRE11. The aim of this study was to determine whether MSI orMRE11mutational status correlates with sensitivity to the PARP inhibitor LT-626 and whether LT-626 synergizes with DNA-damaging chemotherapeutic agents. CRC cells harboring biallelicMRE11mutations were more sensitive to LT-626 and stable overexpression or knock-down of MRE11 in cell lines correlated with sensitivity. Synergism was evident between LT-626 and cisplatin, oxaliplatin and SN-38 suggesting that PARP inhibitors in combination with DNA damaging agents may be a successful strategy for treatment of CRC.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2013.10.034