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The CDK1 inhibitor RO3306 improves the response of BRCA-proficient breast cancer cells to PARP inhibition
Xia Q.; Cai Y.; Peng R.; Wu G.; Shi Y.; Jiang W.
2014
Source PublicationInternational Journal of Oncology
ISSN10196439
Volume44Issue:3Pages:735
AbstractBreast cancer is one of the most common malignancies in women. Approximately 15% of the patients belong to the triple-negative breast cancer (TNBC) group, and have the disadvantage of not benefiting from currently available receptor-targeted systemic therapies. Some cancers in the TNBC group harbor defects in DNA double-strand break repair by homologous recombination (HR), such as BRCA1 dysfunction, and are hypersensitive to poly (ADP-ribose) polymerase (PARP) inhibition. However, only a small fraction of the tumors are BRCA-deficient, and this restricts the therapeutic utility of the PARP inhibitor monotherapy. Cyclin-dependent kinase 1 (CDK1) is necessary not only for BRCA1-mediated S phase checkpoint activation, but also for HR, because it phosphorylates BRCA1 for the efficient formation of BRCA1 foci. In this study, we showed that the combined inhibition of CDK1 and PARP in BRCA-proficient MDA-MB-231 breast cancer cells resulted in dramatically reduced cell growth compared to PARP inhibition alone. Mechanistic investigations revealed that this sensitivity appears to be mediated by sustained DNA damage and inefficient DNA repair triggering mitochondrial-mediated apoptosis as well as autophagy. Our results suggest that CDK1 inhibition represents a plausible strategy for expanding the utility of PARP inhibitors to BRCA-proficient breast cancers.
KeywordBRCA1 Breast cancer Cyclin-dependent kinase 1 Poly (ADP-ribose) polymerase inhibitor
DOI10.3892/ijo.2013.2240
URLView the original
Language英语
The Source to ArticleScopus
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Cited Times [WOS]:17   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
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GB/T 7714
Xia Q.,Cai Y.,Peng R.,et al. The CDK1 inhibitor RO3306 improves the response of BRCA-proficient breast cancer cells to PARP inhibition[J]. International Journal of Oncology,2014,44(3):735.
APA Xia Q.,Cai Y.,Peng R.,Wu G.,Shi Y.,&Jiang W..(2014).The CDK1 inhibitor RO3306 improves the response of BRCA-proficient breast cancer cells to PARP inhibition.International Journal of Oncology,44(3),735.
MLA Xia Q.,et al."The CDK1 inhibitor RO3306 improves the response of BRCA-proficient breast cancer cells to PARP inhibition".International Journal of Oncology 44.3(2014):735.
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