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Poly(ADP-ribose) polymerase activity and inhibition in cancer

Caleb Dulaney1, Samuel Marcrom1, Jennifer Stanley1

  • 1Department of Radiation Oncology, University of Alabama at Birmingham, 1700 6th Avenue South, 176F Hazelrig-Salter Radiation Oncology Center, Room 2232-N, Birmingham, AL 35249-6832, United States.

Seminars in Cell & Developmental Biology
|January 15, 2017
PubMed

Insights

Poly(ADP-ribose) polymerase (PARP) inhibitors exploit cancer

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Genomic instability, driven by faulty DNA repair, is a key cancer characteristic.
  • Poly(ADP-ribose) polymerase (PARP) proteins are crucial for DNA repair pathways like homologous recombination (HR).

Purpose of the Study:

  • To review the cell biology of PARP proteins.
  • To discuss the discovery of synthetic lethality in homologous recombination-deficient cancers.
  • To examine the clinical development and application of PARP inhibitors.

Main Methods:

  • Literature review of PARP biology, DNA repair mechanisms, and clinical trial data.
  • Analysis of synthetic lethality principles in cancer therapy.
  • Examination of FDA-approved PARP inhibitors and ongoing clinical trials.

Main Results:

  • PARP inhibitors demonstrate efficacy in cancers with defective homologous recombination.
  • Five PARP inhibitors are in late-stage clinical development.
  • PARP inhibitors represent a significant advancement in targeted cancer therapy.

Conclusions:

  • PARP inhibitors are effective targeted therapies for specific cancer types.
  • Ongoing research aims to broaden the application of PARP inhibitors.
  • Understanding DNA repair defects is crucial for advancing cancer treatment.
Keywords:
DNA repairPARPPARP inhibitorsPoly(ADP-ribose) polymeraseSynthetic lethality

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