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Article

The CDK1 inhibitor RO3306 improves the response of BRCA-proficient breast cancer cells to PARP inhibition

  • Authors:
    • Qing Xia
    • Yuchen Cai
    • Roujun Peng
    • Guosheng Wu
    • Yanxia Shi
    • Wenqi Jiang
  • View Affiliations / Copyright

    Affiliations: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, P.R. China, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macau SAR, P.R. China
  • Pages: 735-744
    |
    Published online on: December 31, 2013
       https://doi.org/10.3892/ijo.2013.2240
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Abstract

Breast 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.
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Copy and paste a formatted citation
Spandidos Publications style
Xia Q, Cai Y, Peng R, Wu G, Shi Y and Jiang W: The CDK1 inhibitor RO3306 improves the response of BRCA-proficient breast cancer cells to PARP inhibition. Int J Oncol 44: 735-744, 2014.
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, 735-744. https://doi.org/10.3892/ijo.2013.2240
MLA
Xia, Q., Cai, Y., Peng, R., Wu, G., Shi, Y., Jiang, W."The CDK1 inhibitor RO3306 improves the response of BRCA-proficient breast cancer cells to PARP inhibition". International Journal of Oncology 44.3 (2014): 735-744.
Chicago
Xia, Q., Cai, Y., Peng, R., Wu, G., Shi, Y., Jiang, W."The CDK1 inhibitor RO3306 improves the response of BRCA-proficient breast cancer cells to PARP inhibition". International Journal of Oncology 44, no. 3 (2014): 735-744. https://doi.org/10.3892/ijo.2013.2240
Copy and paste a formatted citation
x
Spandidos Publications style
Xia Q, Cai Y, Peng R, Wu G, Shi Y and Jiang W: The CDK1 inhibitor RO3306 improves the response of BRCA-proficient breast cancer cells to PARP inhibition. Int J Oncol 44: 735-744, 2014.
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, 735-744. https://doi.org/10.3892/ijo.2013.2240
MLA
Xia, Q., Cai, Y., Peng, R., Wu, G., Shi, Y., Jiang, W."The CDK1 inhibitor RO3306 improves the response of BRCA-proficient breast cancer cells to PARP inhibition". International Journal of Oncology 44.3 (2014): 735-744.
Chicago
Xia, Q., Cai, Y., Peng, R., Wu, G., Shi, Y., Jiang, W."The CDK1 inhibitor RO3306 improves the response of BRCA-proficient breast cancer cells to PARP inhibition". International Journal of Oncology 44, no. 3 (2014): 735-744. https://doi.org/10.3892/ijo.2013.2240
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