Poly (ADP-ribose) polymerase inhibitor LT-626: Sensitivity correlates with MRE11 mutations and synergizes with platinums and irinotecan in colorectal cancer cells

Highlights • We assess the sensitivity of CRC cell lines to a new PARP inhibitor, LT-626. • Biallelic MRE11 mutations in CRC cells result in increased sensitivity to LT-626. • LT-626 synergizes with platinums and irinotecan in the majority of CRC cell lines. • Combining PARP inhibitors with DNA dama...

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Bibliographic Details
Published in:Cancer letters 2014-02, Vol.343 (2), p.217-223
Main Authors: McPherson, Lisa A, Shen, Yuqiao, Ford, James M
Format: Article
Language:English
Subjects:
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Blotting, Western
Camptothecin - analogs & derivatives
Camptothecin - pharmacology
Cell Line, Tumor
Cisplatin - pharmacology
Colorectal cancer
Colorectal Neoplasms - enzymology
DNA damage
DNA-Binding Proteins - genetics
Drug Synergism
Hematology, Oncology and Palliative Medicine
Heterocyclic Compounds, 3-Ring - chemistry
Heterocyclic Compounds, 3-Ring - pharmacology
Humans
Inhibitory Concentration 50
Irinotecan
MRE11
MRE11 Homologue Protein
MSI
Mutation
PARP inhibitors
Phthalazines - chemistry
Phthalazines - pharmacology
Platinum - pharmacology
Poly(ADP-ribose) Polymerase Inhibitors
Real-Time Polymerase Chain Reaction
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Summary:Highlights • We assess the sensitivity of CRC cell lines to a new PARP inhibitor, LT-626. • Biallelic MRE11 mutations in CRC cells result in increased sensitivity to LT-626. • LT-626 synergizes with platinums and irinotecan in the majority of CRC cell lines. • Combining PARP inhibitors with DNA damaging agents may be a useful strategy for CRC.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2013.10.034