Selective resistance to the PARP inhibitor olaparib in a mouse model for BRCA1-deficient metaplastic breast cancer
- 22 June 2015
- journal article
- research article
- Published by National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 112 (27) , 8409-8414
Abstract
Significance: Poly(ADP-ribose) polymerase (PARP) inhibitors hold promise for patients with breast cancer 1 ( BRCA1 )-associatated cancers but are anticipated to give rise to resistance. We show that mouse mammary tumors resembling BRCA1-associated metaplastic breast carcinoma display intrinsic resistance to the PARP inhibitor olaparib as a result of increased P-glycoprotein drug efflux transporter expression. These findings may have implications for ongoing clinical trials.Keywords
Funding Information
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (93512009)
- Seventh Framework Programme (260791)
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (91814643)
- Association for International Cancer Research (14-0288)
This publication has 38 references indexed in Scilit:
- High MET expression is an adverse prognostic factor in patients with triple-negative breast cancerBritish Journal of Cancer, 2013
- MED12 Controls the Response to Multiple Cancer Drugs through Regulation of TGF-β Receptor SignalingCell, 2012
- An integrated encyclopedia of DNA elements in the human genomeNature, 2012
- Rapid validation of cancer genes in chimeras derived from established genetically engineered mouse modelsBioEssays, 2011
- Met induces mammary tumors with diverse histologies and is associated with poor outcome and human basal breast cancerProceedings of the National Academy of Sciences, 2009
- The Epithelial-to-Mesenchymal Transition and Cancer Stem Cells: A Coalition Against Cancer TherapiesJournal of Mammary Gland Biology and Neoplasia, 2009
- High sensitivity of BRCA1-deficient mammary tumors to the PARP inhibitor AZD2281 alone and in combination with platinum drugsProceedings of the National Academy of Sciences, 2008
- Somatic loss of BRCA1 and p53 in mice induces mammary tumors with features of human BRCA1 -mutated basal-like breast cancerProceedings of the National Academy of Sciences, 2007
- Selective induction of chemotherapy resistance of mammary tumors in a conditional mouse model for hereditary breast cancerProceedings of the National Academy of Sciences, 2007
- BRCA1 dysfunction in sporadic basal-like breast cancerOncogene, 2006