Patient-derived organoids for hepatobiliary cancers: Molecular mechanisms, translational applications and precision therapeutics.

Hepatobiliary cancers are highly heterogeneous malignant tumors, and the drug resistance frequently emerges at advanced stages. Patient-derived organoids (PDOs) are three-dimensional ex vivo cultures. They can reproduce essential biological aspects of primary tumors, and play a key role in personalized oncology. With advances in methodology and technology, PDOs are increasingly being used in hepatobiliary cancer research at both the fundamental and translational levels. This review summarizes recent advances in patient-derived organoids, including culture matrices, microenvironment reconstruction, and organoid-on-chips. We also discuss the applications of PDOs in hepatobiliary cancer modeling and organoid biobank construction. Hepatobiliary cancer organoids hold promise for drug development and may serve as complementary tools for preclinical prediction. Integrating in vitro drug testing, resistance mechanism identification and combination regimen screening, organoid-based workflows can provide platforms for treatment stratification and personalized treatment optimization in hepatobiliary cancers. The incorporation of artificial intelligence may further expand the capabilities of organoid-based platforms. Overall, hepatobiliary cancer organoids represent clinically promising models for overcoming therapeutic resistance and developing personalized treatment strategies. They are powerful tools for precision oncology and clinical translation.