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• W3147655761 endingPage "1656" @default.
• W3147655761 startingPage "1656" @default.
• W3147655761 abstract "The identification of biomarker-driven targeted therapies for patients with triple negative breast cancer (TNBC) remains a major clinical challenge, due to a lack of specific targets. Here, we show that cyclin E, a major regulator of G1 to S transition, is deregulated in TNBC and is associated with mutations in DNA repair genes (e.g., BRCA1/2). Breast cancers with high levels of cyclin E not only have a higher prevalence of BRCA1/2 mutations, but also are associated with the worst outcomes. Using several in vitro and in vivo model systems, we show that TNBCs that harbor either mutations in BRCA1/2 or overexpression of cyclin E are very sensitive to the growth inhibitory effects of AZD-1775 (Wee 1 kinase inhibitor) when used in combination with MK-4837 (PARP inhibitor). Combination treatment of TNBC cell lines with these two agents results in synergistic cell killing due to induction of replicative stress, downregulation of DNA repair and cytokinesis failure that results in increased apoptosis. These findings highlight the potential clinical application of using cyclin E and BRCA mutations as biomarkers to select only those patients with the highest replicative stress properties that may benefit from combination treatment with Wee 1 kinase and PARP inhibitors." @default.
• W3147655761 created "2021-04-13" @default.
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• W3147655761 date "2021-04-01" @default.
• W3147655761 modified "2023-10-10" @default.
• W3147655761 title "Targeting Replicative Stress and DNA Repair by Combining PARP and Wee1 Kinase Inhibitors Is Synergistic in Triple Negative Breast Cancers with Cyclin E or BRCA1 Alteration" @default.
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• W3147655761 cites W1995788690 @default.
• W3147655761 cites W1998727638 @default.
• W3147655761 cites W2003385907 @default.
• W3147655761 cites W2010421788 @default.
• W3147655761 cites W2024950200 @default.
• W3147655761 cites W2031666034 @default.
• W3147655761 cites W2032255236 @default.
• W3147655761 cites W2032522296 @default.
• W3147655761 cites W2036401393 @default.
• W3147655761 cites W2038340312 @default.
• W3147655761 cites W2039442869 @default.
• W3147655761 cites W2042227848 @default.
• W3147655761 cites W2043517613 @default.
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• W3147655761 cites W2081106130 @default.
• W3147655761 cites W2093442957 @default.
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• W3147655761 cites W2111222453 @default.
• W3147655761 cites W2111437716 @default.
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• W3147655761 cites W2125972940 @default.
• W3147655761 cites W2128870032 @default.
• W3147655761 cites W2130410032 @default.
• W3147655761 cites W2137487731 @default.
• W3147655761 cites W2152930453 @default.
• W3147655761 cites W2163294504 @default.
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• W3147655761 cites W2769003179 @default.
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• W3147655761 cites W2801214434 @default.
• W3147655761 cites W2810656127 @default.
• W3147655761 cites W2886477543 @default.
• W3147655761 cites W2889749263 @default.
• W3147655761 cites W2890611180 @default.
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• W3147655761 doi "https://doi.org/10.3390/cancers13071656" @default.
• W3147655761 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8036262" @default.
• W3147655761 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33916118" @default.
• W3147655761 hasPublicationYear "2021" @default.
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