Evolving treatments in high-risk neuroblastoma

ABSTRACT

Introduction: Neuroblastoma is a tumor of the developing sympathetic nervous system. Low and intermediate-risk patients usually have good treatment outcomes, whereas high-risk cases have poorer survival and recurrence rates. This review highlights limitations in the treatment procedure and future therapies in development that may be adopted into clinical practice, compiled from a literature search of scientific papers from the last 30 years including ongoing clinical trials.

Areas covered: Current treatments for high-risk neuroblastoma have shown efficacy in clinical trials; however, this regimen is not effective in preventing relapse in many cases and has high toxicity for pediatric patients. The two main areas of research for new maintenance therapies focus on immunotherapy and gene targeting with molecular therapy. GD2-CAR-T cells and GD2 vaccines have shown efficacy in pre-clinical trials, and MYCN and ALK inhibition target two of the main driver mutations in neuroblastoma potentially offering a highly specific form of therapy.

Expert opinion: Tumor heterogeneity leads to various drivers of neuroblastoma; therefore, combinations of molecular therapies can induce remission, alongside immunotherapy that could lower treatment toxicity. The implementation of ‘liquid biopsies’ could greatly improve genetic characterization of a changing tumor profile (often changing in response to treatment) to inform appropriate therapies.

KEYWORDS:

• Neuroblastoma
• immunotherapy
• gene targeting
• molecular therapies
• clinical trials
• pediatric oncology

Article highlights

• Current treatment protocols for high-risk neuroblastoma are insufficient in preventing relapses in a large proportion of patients.

• Increased understanding of the genetic and molecular characterization of neuroblastoma allows for better prognostication and risk stratification to be performed.

• Immunotherapy and gene targeting with molecular therapy are two fields of innovation that have potential in improving survival outcomes for these patients.

• CAR-T cells or an anti-GD2 vaccine are prospective treatments that can build on the success of the anti-GD2 monoclonal antibodies in targeting the GD2 antigen on neuroblastoma .tumors

• Molecular therapies directed towards inhibiting driver genes could be a more personalized treatment approach alongside immunotherapy that may lower treatment-associated toxicity.

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Declaration of interest

The authors have no 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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.