Application and mechanism of anticancer peptides in organoid models of intrahepatic cholangiocarcinoma.

The clinical manifestations of intrahepatic cholangiocarcinoma (ICC) are non-specific, and few patients qualify for surgical resection at diagnosis, thus limiting treatment options. Anticancer peptides (ACPs) exhibit potent tumour inhibition, minimal side effects, easy modification, and low production costs, making them promising for clinical use. Simultaneously, the development of patient-derived three-dimensional organoids as a novel disease model has enabled the replication of the structure and heterogeneity of solid tumours. These organoids provide valuable tools for understanding disease mechanisms, conducting drug sensitivity tests, and developing targeted therapies. However, ACPs' effect on ICC organoids remain unclear. Therefore, this study aims to explore the potential of ACPs in treating ICC using patient-derived organoids (PDOs). We designed and synthesised a series of ACPs sequences and applied them to PDOs model. The organoid model exhibits histological and genomic characteristics similar to those of maternal tumours. Drug sensitivity revealed that ACPs affected the growth of tumour cells and exerted anticancer effects through direct membrane disruption and indirect induction of apoptosis. In this study, organoids can be used as an in vitro model to evaluate the therapeutic response of ACPs and offer novel insight for the study of ICC.