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Spontaneous regression of neuroblastoma

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Abstract

Neuroblastomas are characterized by heterogeneous clinical behavior, from spontaneous regression or differentiation into a benign ganglioneuroma, to relentless progression despite aggressive, multimodality therapy. Indeed, neuroblastoma is unique among human cancers in terms of its propensity to undergo spontaneous regression. The strongest evidence for this comes from the mass screening studies conducted in Japan, North America and Europe and it is most evident in infants with stage 4S disease. This propensity is associated with a pattern of genomic change characterized by whole chromosome gains rather than segmental chromosome changes but the mechanism(s) underlying spontaneous regression are currently a matter of speculation. There is evidence to support several possible mechanisms of spontaneous regression in neuroblastomas: (1) neurotrophin deprivation, (2) loss of telomerase activity, (3) humoral or cellular immunity and (4) alterations in epigenetic regulation and possibly other mechanisms. It is likely that a better understanding of the mechanisms of spontaneous regression will help to identify targeted therapeutic approaches for these tumors. The most easily targeted mechanism is the delayed activation of developmentally programmed cell death regulated by the tropomyosin receptor kinase A (TrkA) pathway. Pan-Trk inhibitors are currently in clinical trials and so Trk inhibition might be used as the first line of therapy in infants with biologically favorable tumors that require treatment. Alternative approaches consist of breaking immune tolerance to tumor antigens but approaches to telomere shortening or epigenetic regulation are not easily druggable. The different mechanisms of spontaneous neuroblastoma regression are reviewed here, along with possible therapeutic approaches.

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Abbreviations

HLA:

Human leukocyte antigen

INSS:

International Neuroblastoma Staging System

NK:

Natural killer

NGF:

Nerve growth factor

OMS:

Opsomyoclonus syndrome

TAM:

Tumor-associated macrophages

TRK:

Tropomyosin receptor kinase

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Acknowledgements

Some of the information in this review has been presented previously (Brodeur and Bagatell 2014). This work was supported in part by a grant from the National Cancer Institute, Alex’s Lemonade Stand Foundation and the Audrey E. Evans endowed chair (GMB).

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  1. Division of Oncology, Department of Pediatrics, the Children’s Hospital of Philadelphia, University of Pennsylvania/Perelman School of Medicine, Philadelphia, PA, 19104, USA

    Garrett M. Brodeur

  2. Oncology Research, The Children’s Hospital of Philadelphia, CTRB Rm. 3018, 3501 Civic Center Blvd., Philadelphia, PA, 19104-4302, USA

    Garrett M. Brodeur

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Brodeur, G.M. Spontaneous regression of neuroblastoma. Cell Tissue Res 372, 277–286 (2018). https://doi.org/10.1007/s00441-017-2761-2

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