Xu Li, Junyi Lou, Xiaoyu Li, Shibo Tang, Shuang Li, Zining Luo, Jiebin Xie
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.
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.