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Poly(ADP-ribose) polymerase inhibitors in cancer treatment: a clinical perspective

Shahneen K Sandhu1, Timothy A Yap, Johann S de Bono

  • 1The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey SM2 5PT, United Kingdom.

European Journal of Cancer (Oxford, England : 1990)
|November 21, 2009
PubMed

Insights

PARP inhibitors show significant anti-tumor activity in cancers with DNA repair defects, like those in BRCA1/2 carriers. This synthetic lethal approach offers a promising new cancer therapy strategy.

Area of Science:

  • Genomic stability and DNA repair mechanisms.
  • Cancer therapeutics and synthetic lethality.

Background:

  • Genomic stability relies on DNA surveillance and repair.
  • Poly(ADP-ribose) polymerase (PARP) is crucial for DNA damage response.

Purpose of the Study:

  • To review the biological function and rationale for targeting PARP in cancer treatment.
  • To summarize preclinical and clinical data on PARP inhibitors.
  • To discuss the potential and challenges of PARP inhibitors as anticancer agents.

Main Methods:

  • Review of existing preclinical and clinical data on PARP inhibitors.
  • Analysis of the synthetic lethal approach in targeting DNA repair-defective tumors.

Main Results:

  • PARP inhibition demonstrates significant single-agent antitumor activity.
  • Effective therapeutic index observed in homologous DNA repair-defective tumors (e.g., BRCA1/2 mutations).
  • This represents the first successful clinical application of synthetic lethality in cancer therapy.

Conclusions:

  • Targeting DNA repair defects via PARP inhibition is a promising anticancer strategy.
  • PARP inhibitors have broad clinical applicability and potential.
  • Several PARP inhibitors are currently in clinical development.

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