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Tumour-Specific Synthetic Lethality: Targeting BRCA Dysfunction in Ovarian Cancer

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Emerging Therapeutic Targets in Ovarian Cancer

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Abstract

The inheritance of mutations in either BRCA1 or BRCA2 genes is associated with an estimated lifetime risk of developing ovarian cancer of up to 40–50% for BRCA1 mutation carriers and 10–20% for BRCA2 carriers The analysis of BRCA1 and BRCA2 function in DNA repair is leading to new approaches to antitumour therapy for such patients, including the use of poly(ADP)-ribose polymerase (PARP) inhibitors. Such novel agents are selectively lethal to cells lacking functional BRCA1 or BRCA2, with minimal toxicity to cells with normal BRCA function. Early clinical trials have confirmed this finding and shown that PARP inhibitors are well tolerated with substantial antitumour efficacy in ovarian cancer patients with BRCA mutations. The increased understanding of BRCA dysfunction, particularly in high-grade serous ovarian cancers has now led to the testing of these novel therapeutics in broader groups of women with this disease. The stage is now set for this tumour-specific synthetic lethal approach to have a positive impact on women in the gynae-oncology clinic.

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Authors and Affiliations

  1. Drug Development Unit, The Royal Marsden NHS Foundation Trust, Sutton, Surrey, SM2 5PT, UK

    Timothy A. Yap

  2. Section of Medicine, The Institute of Cancer Research, Sutton, Surrey, SM2 5NG, UK

    Timothy A. Yap

  3. Drug Development Unit, Institute of Cancer Research/Royal Marsden Hospital, Sutton, SM2 5PT, UK

    Stan H. Kaye

  4. Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London, SW3 6JB, UK

    Alan Ashworth

  5. Breakthrough Breast Cancer Research Unit, King’s College London, School of Medicine, London, SE1 9RT, UK

    Andrew Tutt

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  1. Timothy A. Yap
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  2. Stan H. Kaye
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  4. Andrew Tutt
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Correspondence to Andrew Tutt .

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Editors and Affiliations

  1. Royal Marsden Hospital, Drug Development Unit, Institute of Cancer Research, Sutton, SM2 5PT, United Kingdom

    Stan Kaye

  2. , Department of Surgery and Cancer, Imperial College London, London, W12 0NN, United Kingdom

    Robert Brown

  3. , Department of Surgery and Cancer, Imperial College, London, W12 0NN, United Kingdom

    Hani Gabra

  4. , Department of Medicine, Royal Marsden Hospital, London, SW3 6JJ, United Kingdom

    Martin Gore

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Yap, T.A., Kaye, S.H., Ashworth, A., Tutt, A. (2011). Tumour-Specific Synthetic Lethality: Targeting BRCA Dysfunction in Ovarian Cancer. In: Kaye, S., Brown, R., Gabra, H., Gore, M. (eds) Emerging Therapeutic Targets in Ovarian Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-7216-3_6

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