Neuroblastoma Clinical Management and Genetic Insights

Neuroblastoma represents the most common paediatric extracranial solid tumour, characterised by marked clinical and genetic heterogeneity. Current management integrates risk stratification based on age, stage, histology and molecular markers to guide multimodal therapy. Low-risk cases may undergo observation or limited surgery, whereas high-risk disease requires intensive induction chemotherapy, surgical resection, high-dose myeloablative therapy with autologous stem cell rescue, radiotherapy, immunotherapy and isotretinoin maintenance. Genetic insights have unveiled key drivers of tumour initiation and progression, including MYCN amplification, ALK activation and 17q chromosomal gains, together with mechanisms of telomere maintenance. Recent advances in genomic profiling and single-cell analyses have reshaped understanding of tumour evolution, revealing early embryonic origins, subclonal diversity and novel targets for precision therapy.

Research from Nature Portfolio

Recent clinical trials have demonstrated that third-generation ALK inhibitors can be safely administered to children and adults with relapsed or refractory ALK-driven neuroblastoma, achieving meaningful response rates both as monotherapy and in combination with topotecan/cyclophosphamide, and informing phase 2 dose recommendations. Deep whole-genome sequencing coupled with molecular clock modelling has shown that neuroblastoma cells originate during the first trimester of fetal development; tumours with prolonged evolutionary periods acquire telomere maintenance mechanisms and exhibit aggressive behaviour, whereas short-evolution tumours often follow a benign course. Pan-cancer genomic analyses across childhood tumours have further defined the spectrum of somatic mutations and structural variants, identifying recurrent alterations in neuroblastoma that inform risk assessment and potential druggable events.

Neuroblastoma Clinical Management and Genetic Insights publication trend

The graph below shows the total number of articles in neuroblastoma clinical management and genetic insights across all publications each year (not limited to Nature Index journals).

Technical terms

ALK alteration: Activating mutations or fusions in the anaplastic lymphoma kinase gene driving oncogenic signalling.

MYCN amplification: Increased copy number of the MYCN oncogene, a hallmark of high-risk neuroblastoma associated with rapid progression.

17q chromosomal gain: Increase in copy number of the long arm of chromosome 17, often linked to adverse prognosis.

Single-cell RNA sequencing: Technique for profiling gene expression in individual cells, revealing intratumour heterogeneity.

Progression-free survival: Interval during and after treatment in which the patient’s disease does not worsen.

References

1. Lorlatinib with or without chemotherapy in ALK-driven refractory/relapsed neuroblastoma: phase 1 trial results. Nature Medicine (2023).
2. Neuroblastoma arises in early fetal development and its evolutionary duration predicts outcome. Nature Genetics (2023).
3. The landscape of genomic alterations across childhood cancers. Nature (2018).
4. Irinotecan and temozolomide in combination with dasatinib and rapamycin versus irinotecan and temozolomide for patients with relapsed or refractory neuroblastoma (RIST-rNB-2011): a multicentre, open-label, randomised, controlled, phase 2 trial. The Lancet Oncology (2024).
5. Integrative analysis of neuroblastoma by single-cell RNA sequencing identifies the NECTIN2-TIGIT axis as a target for immunotherapy. Cancer Cell (2024).
6. IGF2BP1 induces neuroblastoma via a druggable feedforward loop with MYCN promoting 17q oncogene expression. Molecular Cancer (2023).