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The clinical development of inhibitors of poly(ADP-ribose) polymerase

H Calvert1, A Azzariti

  • 1Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK.

Annals of Oncology : Official Journal of the European Society for Medical Oncology
|February 3, 2011
PubMed

Insights

Poly(ADP-ribose) polymerase (PARP) inhibitors show promise for treating BRCA-mutated hereditary breast cancers. These drugs exploit synthetic lethality, selectively targeting cancer cells with DNA repair deficiencies for effective cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • DNA repair inhibitors are investigated as cancer therapeutics.
  • Poly(ADP-ribose) polymerase (PARP) inhibitors are crucial for BRCA1/BRCA2-mutated hereditary breast cancers.

Purpose of the Study:

  • To review the development and clinical evaluation of PARP inhibitors.
  • To discuss their role in treating BRCA-related cancers.

Main Methods:

  • In vitro studies assessing cytotoxicity of PARP inhibitors on cell lines with and without BRCA mutations.
  • Clinical evaluation of PARP inhibitors as single agents in BRCA-related tumors.

Main Results:

  • PARP inhibitors demonstrate high cytotoxicity in BRCA-mutated cell lines, minimal toxicity in wild-type lines.
  • Remarkable single-agent activity observed in clinical trials for BRCA-related tumors.

Conclusions:

  • PARP inhibitors leverage synthetic lethality, targeting cancer cells unable to repair DNA double-strand breaks.
  • These inhibitors represent a significant advancement in treating hereditary breast cancers and have potential for future development.

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