Royal College of Surgeons in Ireland
Fitzgerald 2022 Targeting the apoptosis pathway to treat tumours of the paediatric nervous.pdf (1.3 MB)

Targeting the apoptosis pathway to treat tumours of the paediatric nervous system

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journal contribution
posted on 2023-03-13, 16:49 authored by Marie-Claire Fitzgerald, Philip J O’Halloran, Niamh ConnollyNiamh Connolly, Brona MurphyBrona Murphy
New, more effective therapeutics are required for the treatment of paediatric cancers. Current treatment protocols of cytotoxic treatments including chemotherapy trigger cancer-cell death by engaging the apoptosis pathway, and chemotherapy efficacy is frequently impeded by apoptosis dysregulation. Apoptosis dysregulation, through genetic or epigenetic mechanisms, is a feature of many cancer types, and contributes to reduced treatment response, disease progression and ultimately treatment resistance. Novel approaches are required to overcome dysregulated apoptosis signalling, increase the efficacy of cancer treatment and improve patient outcomes. Here, we provide an insight into current knowledge of how the apoptosis pathway is dysregulated in paediatric nervous system tumours, with a focus on TRAIL receptors, the BCL-2 proteins and the IAP family, and highlight preclinical evidence demonstrating that pharmacological manipulation of the apoptosis pathway can restore apoptosis signalling and sensitise cancer cells to treatment. Finally, we discuss the potential clinical implications of these findings.


National Children’s Research Centre, Crumlin, grant number NCRC A/18/1

Irish Association for Cancer Research (IACR Educational Grant)



The original article is available at

Published Citation

Fitzgerald MC, O'Halloran PJ, Connolly NMC, Murphy BM. Targeting the apoptosis pathway to treat tumours of the paediatric nervous system. Cell Death Dis. 2022;13(5):460.

Publication Date

14 May 2022

PubMed ID



  • Centre for Systems Medicine
  • Physiology and Medical Physics

Research Area

  • Neurological and Psychiatric Disorders
  • Surgical Science and Practice
  • Cancer


Nature Pub. Group


  • Published Version (Version of Record)