Advances in pharmacotherapy for neuroblastoma

ABSTRACT

Introduction

Neuroblastoma is the most prevalent cancer type diagnosed within the first year after birth and accounts for 15% of deaths from pediatric cancer. Despite the improvements in survival rates of patients with neuroblastoma, the incidence of the disease has increased over the last decade. Neuroblastoma tumor cells harbor a vast range of variable and heterogeneous histochemical and genetic alterations which calls for the need to administer individualized and targeted therapies to induce tumor regression in each patient.

Areas covered

This paper provides reviews the recent clinical trials which used chemotherapeutic and/or targeted agents as either monotherapies or in combination to improve the response rate in patients with neuroblastoma, and especially high-risk neuroblastoma. It also reviews some of the prominent preclinical studies which can provide the rationale for future clinical trials.

Expert opinion

Although some distinguished advances in pharmacotherapy have been made to improve the survival rate and reduce adverse events in patients with neuroblastoma, a more comprehensive understanding of the mechanisms of tumorigenesis, resistance to therapies or relapse, identifying biomarkers of response to each specific drug, and developing predictive preclinical models of the tumor can lead to further breakthroughs in the treatment of neuroblastoma.

KEYWORDS:

• Neuroblastoma
• chemotherapy
• targeted therapy
• emerging drugs
• drug development
• alk inhibitors
• immunotherapy

Article highlights

• Neuroblastoma is the third most common pediatric cancer, and the most common cancer diagnosed in the first year of life and accounts for 7% of cancer cases in this age group.

• Modifications such as MYC-N proto-oncogene amplification, loss of heterozygosity of 1p or 11q, or 17q chromosome arm translocations, or hyper-activation or over-expression of ALK are defined as characteristics of unfavorable tumors.

• Over the last years, understanding of exact cellular pathways has led to the development of targeted drug monotherapy or in combination with chemotherapy, radiotherapy, or other targeted agents to improve the response rate of patients with neuroblastoma.

• Retinoids and their synthetic congeners which can trigger differentiation in tumor cells and immunotherapeutic approaches such as anti-GD2 antibodies, vaccines, and CAR-T cell therapy have shown promising results in the treatment of patients with neuroblastoma.

• Future potential therapeutic advances would constitute tailoring an individualized treatment regimen of targeted agents based on the tumor’s biological profile, and the development of directed therapies for emerging targets such as lncRNAs, miRNAs, and components involved in EMT.

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

This manuscript was not funded.