High sensitivity of BRCA1-deficient mammary tumors to the PARP inhibitor AZD2281 alone and in combination with platinum drugs

Whereas target-specific drugs are available for treating ERBB2-overexpressing and hormone receptor-positive breast cancers, no tailored therapy exists for hormone receptor- and ERBB2-negative ("triple-negative") mammary carcinomas. Triple-negative tumors account for 15% of all breast cancers and frequently harbor defects in DNA double-strand break repair through homologous recombination (HR), such as BRCA1 dysfunction. The DNA-repair defects characteristic of BRCA1-deficient cells confer sensitivity to poly(ADP-ribose) polymerase 1 (PARP1) inhibition, which could be relevant to treatment of triple-negative tumors. To evaluate PARP1 inhibition in a realistic in vivo setting, we tested the PARP inhibitor AZD2281…

• NS
  National Science Foundation
• EC
  European Commission
• SN
  Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung

  Award: 104429
• NO
  Nederlandse Organisatie voor Wetenschappelijk Onderzoek
• KK
  KWF Kankerbestrijding

  Award: 2006-3566
• NI
  National Institutes of Health