Differentiating Neuroblastoma: A Systematic Review of the Retinoic Acid, Its Derivatives, and Synergistic Interactions.

Nadiya Bayeva,Erin Coll,Olga Piskareva

doi:10.3390/jpm11030211

Abstract

A neuroblastoma (NB) is a solid paediatric tumour arising from undifferentiated neuronal cells. Despite the recent advances in disease management and treatment, it remains one of the leading causes of childhood cancer deaths, thereby necessitating the development of new therapeutic agents and regimens. Retinoic acid (RA), a vitamin A derivative, is a promising agent that can induce differentiation in NB cells. Its isoform, 13-cis RA or isotretinoin, is used in NB therapy; however, its effectiveness is limited to treating a minimal residual disease as maintenance therapy. As such, research focuses on RA derivatives that might increase the anti-NB action or explores the potential synergy between RA and other classes of drugs, such as cellular processes mediators, epigenetic modifiers, and immune modulators. This review summarises the in vitro, in vivo, and clinical data of RA, its derivatives, and synergising compounds, thereby establishing the most promising RA derivatives and combinations of RA for further investigation.

Highlights

A neuroblastoma (NB) is an aggressive heterogeneous solid tumour arising from the sympathetic nervous system’s precursor or immature cells during embryonic development or early postnatal life [1,2]
Three-hundred and thirty-one articles were yielded initially through an online database search, while an additional 15 papers were identified through examining the references of the review papers
We attempted to systematically review current efforts to differentiate neuroblastoma directly targeting the classical retinoic acid pathway and indirectly by mimicking their downstream effects of Retinoic acid (RA) published from 1 January 1980 to 1 July 2020

Summary

Introduction

A neuroblastoma (NB) is an aggressive heterogeneous solid tumour arising from the sympathetic nervous system’s precursor or immature cells during embryonic development or early postnatal life [1,2]. NB is highly heterogenic clinically, and the disease progression and outcome depend on many risk factors, including the age at diagnosis, tumour size and localisation, histopathologic classification (e.g., stroma cell differentiation), genetic abnormalities, and MYCN status [1]. Diagnosed patients are stratified into “risk groups” based on the combination of the listed risk factors and the likelihood of developing an aggressive form of neuroblastoma. Despite recent treatment advances, the patients’ five-year survival rate in the high-risk group and with refractory neuroblastoma remains 40–50% [7]

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Conclusion