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Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase

Author

Listed:
  • Helen E. Bryant

    (University of Sheffield, Medical School)

  • Niklas Schultz

    (Microbiology and Toxicology, Arrhenius Laboratory, Stockholm University)

  • Huw D. Thomas

    (University of Newcastle upon Tyne, Medical School)

  • Kayan M. Parker

    (University of Sheffield, Medical School)

  • Dan Flower

    (University of Sheffield, Medical School)

  • Elena Lopez

    (University of Sheffield, Medical School)

  • Suzanne Kyle

    (University of Newcastle upon Tyne, Medical School)

  • Mark Meuth

    (University of Sheffield, Medical School)

  • Nicola J. Curtin

    (University of Newcastle upon Tyne, Medical School)

  • Thomas Helleday

    (University of Sheffield, Medical School
    Microbiology and Toxicology, Arrhenius Laboratory, Stockholm University)

Abstract

Cancer therapy: stop PARP The discovery that BRCA1/2 mutant cells (defective in the homologous recombination pathway of DNA repair) are spectacularly sensitive to inhibition of the enzyme PARP (involved in base excision repair) suggests a new, low toxicity, approach to the treatment of women with breast cancers caused by BRCA mutations. As the PARP inhibitors have no effect on cells with functional homologous recombination, the hope is that the treatment will be specific for breast cancer cells. PARP-inhibiting chemotherapeutics may be able to make use of a ‘synthetic lethal’ effect as an alternative to conventional nonspecific cytotoxic anticancer treatments.

Suggested Citation

  • Helen E. Bryant & Niklas Schultz & Huw D. Thomas & Kayan M. Parker & Dan Flower & Elena Lopez & Suzanne Kyle & Mark Meuth & Nicola J. Curtin & Thomas Helleday, 2005. "Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase," Nature, Nature, vol. 434(7035), pages 913-917, April.
    • Handle: RePEc:nat:nature:v:434:y:2005:i:7035:d:10.1038_nature03443
    DOI: 10.1038/nature03443
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    Cited by:

    1. Takuya Tsujino & Tomoaki Takai & Kunihiko Hinohara & Fu Gui & Takeshi Tsutsumi & Xiao Bai & Chenkui Miao & Chao Feng & Bin Gui & Zsofia Sztupinszki & Antoine Simoneau & Ning Xie & Ladan Fazli & Xuesen, 2023. "CRISPR screens reveal genetic determinants of PARP inhibitor sensitivity and resistance in prostate cancer," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    2. Jun Dai & Shuyu Zheng & Matías M. Falco & Jie Bao & Johanna Eriksson & Sanna Pikkusaari & Sofia Forstén & Jing Jiang & Wenyu Wang & Luping Gao & Fernando Perez-Villatoro & Olli Dufva & Khalid Saeed & , 2024. "Tracing back primed resistance in cancer via sister cells," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    3. Lee Shaashua & Aviad Ben-Shmuel & Meirav Pevsner-Fischer & Gil Friedman & Oshrat Levi-Galibov & Subhiksha Nandakumar & Debra Barki & Reinat Nevo & Lauren E. Brown & Wenhan Zhang & Yaniv Stein & Chen L, 2022. "BRCA mutational status shapes the stromal microenvironment of pancreatic cancer linking clusterin expression in cancer associated fibroblasts with HSF1 signaling," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    4. Sidrah Shah & Alison Cheung & Mikolaj Kutka & Matin Sheriff & Stergios Boussios, 2022. "Epithelial Ovarian Cancer: Providing Evidence of Predisposition Genes," IJERPH, MDPI, vol. 19(13), pages 1-14, July.

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