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Targeting Tankyrase 1 as a therapeutic strategy for BRCA-associated cancer

Oncogene volume 28, pages 1465–1470 (2009)Cite this article

Abstract

The BRCA1 and BRCA2 proteins are involved in the maintenance of genome stability and germ-line loss-of-function mutations in either BRCA1 or BRCA2 strongly predispose carriers to cancers of the breast and other organs. It has been demonstrated previously that inhibiting elements of the cellular DNA maintenance pathways represents a novel therapeutic approach to treating tumors in these individuals. Here, we show that inhibition of the telomere-associated protein, Tankyrase 1, is also selectively lethal with BRCA deficiency. We also demonstrate that the selectivity caused by inhibition of Tankyrase 1 is associated with an exacerbation of the centrosome amplification phenotype associated with BRCA deficiency. We propose that inhibition of Tankyrase 1 could be therapeutically exploited in BRCA-associated cancers.

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Acknowledgements

This work was funded by Breakthrough Breast Cancer and Cancer Research UK. We thank Jill Williamson and Dave Robertson for assistance with karyotyping and microscopy, respectively.

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Authors and Affiliations

  1. Cancer Research UK Gene Function and Regulation Group, Institute of Cancer Research, London, UK

    N McCabe & A Ashworth

  2. The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London, UK

    N McCabe, M A Cerone, C J Lord & A Ashworth

  3. Division of Molecular Biotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan

    T Ohishi & H Seimiya

Authors
  1. N McCabe
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  2. M A Cerone
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  3. T Ohishi
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  4. H Seimiya
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  5. C J Lord
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  6. A Ashworth
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Corresponding author

Correspondence to A Ashworth.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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McCabe, N., Cerone, M., Ohishi, T. et al. Targeting Tankyrase 1 as a therapeutic strategy for BRCA-associated cancer. Oncogene 28, 1465–1470 (2009). https://doi.org/10.1038/onc.2008.483

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  • DOI: https://doi.org/10.1038/onc.2008.483

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