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Cellular and Molecular Biology

Cellular senescence in neuroblastoma

British Journal of Cancer volume 126, pages 1529–1538 (2022)Cite this article

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Abstract

Neuroblastoma is a tumour that arises from the sympathoadrenal lineage occurring predominantly in children younger than five years. About half of the patients are diagnosed with high-risk tumours and undergo intensive multi-modal therapy. The success rate of current treatments for high-risk neuroblastoma is disappointingly low and survivors suffer from multiple therapy-related long-term side effects. Most chemotherapeutics drive cancer cells towards cell death or senescence. Senescence has long been considered to represent a terminal non-proliferative state and therefore an effective barrier against tumorigenesis. This dogma, however, has been challenged by recent observations that infer a much more dynamic and reversible nature for this process, which may have implications for the efficacy of therapy-induced senescence-oriented treatment strategies. Neuroblastoma cells in a dormant, senescent-like state may escape therapy, whilst their senescence-associated secretome may promote inflammation and invasiveness, potentially fostering relapse. Conversely, due to its distinct molecular identity, senescence may also represent an opportunity for the development of novel (combination) therapies. However, the limited knowledge on the molecular dynamics and diversity of senescence signatures demands appropriate models to study this process in detail. This review summarises the molecular knowledge about cellular senescence in neuroblastoma and investigates current and future options towards therapeutic exploration.

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Fig. 1: An overview of cellular senescence inducers and its dynamic impact on tumour growth.

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Acknowledgements

The authors would like to thank Joshua Robert Goulding from the Department of Biomolecular Medicine at Center for Medical Genetics Ghent for providing English language editing and review assistance.

Funding

This research was supported by ‘Kom op tegen Kanker’ (Stand up to Cancer), the Flemish Cancer Society (research grant to F. Speleman); Kinderkankerfonds, the non-profit childhood cancer foundation under Belgian law (research grant to F. Speleman); Olivia Hendrickx Research Fund vzw. The following authors B. Decaesteker (1238420 N) and S. Vanhauwaert (12U4718N) are supported by an FWO grant.

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Authors and Affiliations

  1. Laboratory of Cell Biology and Histology, Department of Veterinary Sciences, University of Antwerp, Universiteitsplein 1, Antwerp, 2610, Belgium

    Sofia Zanotti & Winnok H. De Vos

  2. Department of Biomolecular Medicine, Ghent University, Corneel Heymanslaan 10, Ghent, 9000, Belgium

    Sofia Zanotti, Bieke Decaesteker, Suzanne Vanhauwaert, Bram De Wilde & Frank Speleman

  3. Cancer Research Institute Ghent (CRIG), Ghent, 9000, Belgium

    Sofia Zanotti, Bieke Decaesteker, Suzanne Vanhauwaert & Frank Speleman

  4. Department of Internal Medicine and Pediatrics, Ghent University, Corneel Heymanslaan 10, Ghent, 9000, Belgium

    Bram De Wilde

  5. Department of Pediatric Hematology Oncology and Stem Cell Transplantation, Ghent University Hospital, Ghent, 9000, Belgium

    Bram De Wilde

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  1. Sofia Zanotti
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Contributions

SZ, WHDV and FS: conceptualisation. SZ, BD and SV: literature research and preparation of the first draft of the paper. SZ: table content and figure design. BD, BDW, WHDV and FS: critical revision and editing. All authors have read and agreed to the published version of the paper.

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Correspondence to Frank Speleman.

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Zanotti, S., Decaesteker, B., Vanhauwaert, S. et al. Cellular senescence in neuroblastoma. Br J Cancer 126, 1529–1538 (2022). https://doi.org/10.1038/s41416-022-01755-0

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