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Opportunities and hurdles in the treatment of BRCA1-related breast cancer

Oncogene volume 33, pages 3753–3763 (2014)Cite this article

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Abstract

BRCA1 functions as a classical tumor suppressor in breast and ovarian cancer. While the role of BRCA1 in homology-directed repair of DNA double-strand breaks contributes to its tumor suppressive activity, it also renders BRCA1-deficient cells highly sensitive to DNA-damaging agents. Although BRCA1 deficiency is therefore considered to be an attractive therapeutic target, re-activation of BRCA1 by secondary mutations has been shown to cause therapy resistance. In this review, we will assess the role of BRCA1 in both hereditary and sporadic breast cancer and discuss how different functionalities of the BRCA1 protein can contribute to its tumor suppressor function. In addition, we will discuss how this knowledge on BRCA1 function can help to overcome the hurdles encountered in the clinic and improve current treatment strategies for patients with BRCA1-related breast cancer.

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Acknowledgements

We thank Peter Bouwman and Sven Rottenberg for helpful discussions and comments on the manuscript. This work was supported by grants from the European Union, the TI Center for Translational Molecular Medicine (CTMM), the Netherlands Organization for Scientific Research (NWO), the Cancer Systems Biology Center, the Cancer Genomics Centre Netherlands and the Dutch Cancer Society (KWF).

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Drost, R., Jonkers, J. Opportunities and hurdles in the treatment of BRCA1-related breast cancer. Oncogene 33, 3753–3763 (2014). https://doi.org/10.1038/onc.2013.329

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