Emerging therapeutic targets for neuroblastoma

ABSTRACT

Introduction

Neuroblastoma (NB) is the prime cancer of infancy, and accounts for 9% of pediatric cancer deaths. While children diagnosed with clinically stable NB experience a complete cure, those with high-risk disease (HR-NB) do not recover, despite intensive therapeutic strategies. Development of novel and effective targeted therapies is needed to counter disease progression, and to benefit long-term survival of children with HR-NB.

Areas covered

Recent studies (2017–2020) pertinent to NB evolution are selectively reviewed to recognize novel and effective therapeutic targets. The prospective and promising therapeutic targets/strategies for HR-NB are categorized into (a) targeting oncogene-like and/or reinforcing tumor suppressor (TS)-like lncRNAs; (b) targeting oncogene-like microRNAs (miRs) and/or mimicking TS-miRs; (c) targets for immunotherapy; (d) targeting epithelial-to-mesenchymal transition and cancer stem cells; (e) novel and beneficial combination approaches; and (f) repurposing drugs and other strategies in development.

Expert opinion

It is highly unlikely that agents targeting a single candidate or signaling will be beneficial for an HR-NB cure. We must develop efficient drug deliverables for functional targets, which could be integrated and advance clinical therapy. Fittingly, the looming evidence indicated an aggressive evolution of promising novel and integrative targets, development of efficient drugs, and improvised strategies for HR-NB treatment.

KEYWORDS:

• Emerging therapeutics
• high-risk Neuroblastoma
• long non-coding RNAs
• micro RNAs
• immunotherapy
• novel combinations
• novel drugs

Article highlights

• Novel and improved therapeutic schemes are required to counter unacceptable survival rates in children with high-risk neuroblastoma (HR-NB)

• Oncogene-like and tumor suppressor lncRNAs serves as emerging therapeutic targets for NB

• OncomiRs - TS-miRS’ modulation and coordinated functions dictates NB pathogenesis

• lncRNAs sponge multiple miRs, activating oncogenes and drivers that converge in NB pathogenesis

• Novel targets for immunotherapy indicates a promising strategy for the treatment of HR-NB

• Targeting EMT and CSC stemness maintenance is highly beneficial for progressive disease

• Combination strategies and/or repurposing clinical drugs are highly effective for HR-NB.

This box summarizes key points contained in the article.

Acknowledgments

The authors acknowledge the OUHSC Staff Editor (Ms. Kathy Kyler) for the help in critically reviewing this manuscript.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

Supported by the National Institutes of Health [NIH-P20GM103639]; and Oklahoma Center for the Advancement of Science and Technology [OCAST-HR19-045].