Abstract
Background
Hepatoblastoma (HB) is the most common childhood liver malignancy, yet its research trajectory and trial landscape remain uncharacterized.
Methods
We analyzed 219 trials from 16 international registries and 2,635 PubMed publications (2005–2024) using joinpoint regression, Gini coefficient, and diversity indices.
Results
Trial activity peaked in 2013 and 2016, driven by risk-stratified protocols and the emergence of targeted therapies. Phase III/IV trials were scarce. Cisplatin dominated drug utilization, with 54–80% resistance after 4–5 cycles. Targets concentrated on VEGFR/TOP1/RET/BRAF, while Hippo/YAP and immune checkpoints were underrepresented despite mechanistic relevance. AFP (n=607), CTNNB1 (>80% mutation frequency), TP53, AKT1, and MYC were top-reported genes. Geographic inequality correlated with healthcare infrastructure rather than disease burden.
Conclusions
The HB research ecosystem exhibits robust early-phase activity but constrained late-stage validation, narrow target diversity, and geographic inequity. Multi-omics integration and pediatric-specific preclinical platforms are urgently needed to bridge translational gaps.