The role of personalised medicine in treating high-risk neuroblastoma in paediatric patients

Neuroblastoma (NB) is one of the most challenging paediatric malignancies, accounting for 15% of childhood cancer-related deaths. It is characterised by a high heterogeneity ranging from spontaneous regression to high frequency of metastatic disease at diagnosis. Although current treatment strategies, including chemotherapy, surgery and radiotherapy, have improved outcomes, recurrence often occurs in high-risk NB patients, thus affecting overall survival. In this context, personalised medicine is emerging as a promising approach taking advantage of predictive biomarkers to refine risk stratification and to predict treatment response, together with the development of innovative treatments for high-risk NB. This review summarises the landscape of biomarkers in NB, focusing on genomic, transcriptomic, proteomic, and metabolomic signatures associated with aggressive disease biology, therapeutic resistance, and clinical outcome. We highlight how improved patient stratification could help to identify actionable targets resulting in innovative therapeutic strategies. These include GD2-directed immunotherapy, CAR-T and CAR-NK cell approaches, and pathway-directed agents targeting mainly ALK, and MYCN-associated dependencies. Ultimately, the transition from standardised protocols to a systematic integration of multidimensional biomarker profiles with next-generation therapies promises to transform the clinical management of high-risk NB. Addressing the biological complexity of NB ensures more effective and less toxic interventions, paving the way for personalised therapeutic approaches aimed at preventing relapse in high-risk cases and significantly improving long-term survival.