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Neuroblastoma pathogenesis: deregulation of embryonic neural crest development

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Abstract

Neuroblastoma (NB) is an aggressive pediatric cancer that originates from neural crest tissues of the sympathetic nervous system. NB is highly heterogeneous both from a clinical and a molecular perspective. Clinically, this cancer represents a wide range of phenotypes ranging from spontaneous regression of 4S disease to unremitting treatment-refractory progression and death of high-risk metastatic disease. At a cellular level, the heterogeneous behavior of NB likely arises from an arrest and deregulation of normal neural crest development. In the present review, we summarize our current knowledge of neural crest development as it relates to pathways promoting ‘stemness’ and how deregulation may contribute to the development of tumor-initiating CSCs. There is an emerging consensus that such tumor subpopulations contribute to the evolution of drug resistance, metastasis and relapse in other equally aggressive malignancies. As relapsed, refractory disease remains the primary cause of death for neuroblastoma, the identification and targeting of CSCs or other primary drivers of tumor progression remains a critical, clinically significant goal for neuroblastoma. We will critically review recent and past evidence in the literature supporting the concept of CSCs as drivers of neuroblastoma pathogenesis.

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Authors and Affiliations

  1. Department of Pediatrics, Section of Hematology-Oncology, Texas Children’s Cancer Center, Houston, TX, 77030, USA

    Julie A. Tomolonis, Saurabh Agarwal & Jason M. Shohet

  2. Medical Scientist Training Program (MSTP), Baylor College of Medicine, Houston, TX, 77030, USA

    Julie A. Tomolonis

  3. Translational Biology & Molecular Medicine (TBMM) Graduate Program, Baylor College of Medicine, Houston, TX, 77030, USA

    Julie A. Tomolonis

  4. Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, 77030, USA

    Saurabh Agarwal & Jason M. Shohet

  5. Neuroblastoma Research Program, Texas Children’s Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA

    Jason M. Shohet

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  1. Julie A. Tomolonis
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Correspondence to Jason M. Shohet.

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The authors are supported by grants from NIH (R01 CA174808), Alex’s Lemonade Stand Foundation, Gilson-Longenbaugh Foundation, the Children’s Neuroblastoma Research Foundation, the Wipe Out Kids’ Cancer Foundation, the St. Baldrick’s Foundation and the Cancer Preventions & Research Institute of Texas (CPRIT RP160283).

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Tomolonis, J.A., Agarwal, S. & Shohet, J.M. Neuroblastoma pathogenesis: deregulation of embryonic neural crest development. Cell Tissue Res 372, 245–262 (2018). https://doi.org/10.1007/s00441-017-2747-0

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