6-thioguanine selectively kills BRCA2-defective tumors and overcomes PARP inhibitor resistance.

  title={6-thioguanine selectively kills BRCA2-defective tumors and overcomes PARP inhibitor resistance.},
  author={Natalia Issaeva and Huw D. Thomas and Tatjana Djureinovic and Janneke E. Jaspers and Ivaylo Stoimenov and Suzanne Kyle and Nicholas M Pedley and Ponnari Gottipati and Rafal Zur and Kate M Sleeth and Vicky Chatzakos and Evan A. Mulligan and Cecilia Lundin and Evgenia Gubanova and Ariena Kersbergen and Adrian L. Harris and Ricky A. Sharma and Sven Rottenberg and Nicola J Curtin and Thomas Helleday},
  journal={Cancer research},
  volume={70 15},
Familial breast and ovarian cancers are often defective in homologous recombination (HR) due to mutations in the BRCA1 or BRCA2 genes. Cisplatin chemotherapy or poly(ADP-ribose) polymerase (PARP) inhibitors were tested for these tumors in clinical trials. In a screen for novel drugs that selectively kill BRCA2-defective cells, we identified 6-thioguanine (6TG), which induces DNA double-strand breaks (DSB) that are repaired by HR. Furthermore, we show that 6TG is as efficient as a PARP inhibitor… CONTINUE READING

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