Abstract
Paediatric medulloblastoma is the most common malignant brain tumour in children, exhibiting substantial biological heterogeneity that drives variable treatment outcomes. Despite advances in multimodal therapy, treatment-related morbidity remains a critical concern, underscoring the need for biomarkers to guide precision therapy. This review synthesises current knowledge on biomarkers of treatment response, encompassing molecular, epigenetic, transcriptomic, protein, and imaging-based markers. WNT-activated tumours show excellent prognosis and are candidates for therapy de-escalation; SHH-driven tumours demonstrate age-dependent outcomes influenced by TP53 status; Group 3 tumours carry the poorest prognosis; and Group 4 tumours display highly variable outcomes. DNA methylation profiles, transcriptional programs, and non-coding RNAs provide additional predictive insights. Protein biomarkers and advanced imaging, including liquid biopsy and radiomics, offer minimally invasive approaches for real-time monitoring of treatment efficacy. The review also addresses challenges such as intra-tumour heterogeneity, limited tissue availability, technical variability, and ethical considerations in paediatric oncology. Finally, we explore future directions, highlighting integrative, longitudinal, and ethically grounded biomarker strategies that have the potential to optimise therapy, minimise long-term toxicity, and improve both survival and quality of life for children with medulloblastoma.