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Poly(ADP-ribose) polymerase inhibitors in Ewing sarcoma

Britta Vormoor1, Nicola J Curtin

  • 1aNewcastle Cancer Centre at the Northern Institute for Cancer Research, Newcastle University bGreat North Children's Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.

Current Opinion in Oncology
|May 21, 2014
PubMed
Abstract

Insights

Poly(ADP-ribose) polymerase (PARP) inhibitors show promise for Ewing sarcoma treatment. Preclinical data suggest combining PARP inhibitors with chemotherapy or radiotherapy is more effective than single-agent therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Ewing sarcoma cells exhibit sensitivity to poly(ADP-ribose) polymerase (PARP) inhibition.
  • PARP plays a crucial role in DNA repair and transcription regulation.
  • The Ewing sarcoma oncoprotein EWS-FLI1 may interact with PARP-1, influencing its expression and transcriptional activity.

Purpose of the Study:

  • To review PARP function and the development of PARP inhibitors (PARPi).
  • To examine the evidence for targeting PARP in Ewing sarcoma treatment.
  • To describe ongoing and emerging clinical trials of PARPi in Ewing sarcoma.

Main Methods:

  • Literature review of PARP function, PARPi development, and Ewing sarcoma research.
  • Analysis of preclinical data on PARPi efficacy in Ewing sarcoma models.
  • Overview of current clinical trials involving PARPi for Ewing sarcoma.

Main Results:

  • PARP inhibitors offer dual rationales for Ewing sarcoma treatment: disrupting EWS-FLI1 interaction and potentiating chemotherapy/radiotherapy.
  • A Phase I clinical trial of single-agent PARPi did not yield significant responses.
  • Preclinical studies demonstrate promising results for combining PARPi with chemotherapy or radiotherapy.

Conclusions:

  • Initial enthusiasm for single-agent PARPi in Ewing sarcoma is tempered by clinical trial outcomes.
  • Emerging preclinical evidence strongly supports the clinical investigation of PARPi in combination therapies for Ewing sarcoma.

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