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09:51

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Autophagy impairs the sensitivity of Ewing sarcoma cells to PARP inhibitors

Julia Clausen1,2, Daniela Kocher1,2,3, Hauke M Schadwinkel4,5,6

  • 1Department of Paediatric and Adolescent Medicine, Jena University Hospital, Friedrich Schiller University Jena, Jena, Germany.

Cancer Chemotherapy and Pharmacology
|May 29, 2026
PubMed
Abstract

Insights

Autophagy promotes resistance to PARP inhibitors (PARPi) in Ewing sarcoma. Targeting autophagy may enhance PARPi effectiveness against this cancer.

Area of Science:

  • Oncology
  • Cell Biology

Background:

  • Poly (ADP-ribose) polymerase inhibitors (PARPi) show preclinical efficacy in Ewing sarcoma.
  • Clinical trials with olaparib revealed limited responses, indicating resistance mechanisms.
  • Autophagy is a known resistance mechanism in other cancers.

Purpose of the Study:

  • Investigate the role of autophagy in PARPi resistance in Ewing sarcoma.
  • Determine the impact of autophagy modulation on PARPi effectiveness.

Main Methods:

  • Assessed PARPi (olaparib, veliparib) effects on Ewing sarcoma cell lines (WE-68, SK-ES-1) using flow cytometry.
  • Measured autophagy levels with Cyto-ID and cytotoxic effects via cell death and mitochondrial membrane potential analysis.
  • Separated cells into low, medium, and high autophagy subpopulations via cell sorting.

Main Results:

  • PARPi induced both autophagy and cell death in Ewing sarcoma cells.
  • Higher autophagy levels correlated with reduced PARPi-induced cell death.
  • Cells with high autophagy were significantly less responsive to PARPi treatment.

Conclusions:

  • Autophagy influences the anticancer activity of PARPi in Ewing sarcoma.
  • Autophagy represents a resistance mechanism to PARPi in this cancer type.
Keywords:
AutophagyCeliparibCell sortingCyto-IDEwing sarcomaOlaparibPARP

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