Organoid-based drug screening identifies homoharringtonine as a therapeutic agent for anaplastic thyroid cancer via TFEB-mediated lysosomal dysfunction.

ABSTRACT:

Purpose

Anaplastic thyroid cancer (ATC) is a rare but aggressive malignancy with unmet clinical needs for novel therapeutic agents. Most prior studies have relied on limited ATC cell lines, which fail to recapitulate tumor heterogeneity. This study aimed to discover novel agent for ATC via patient-derived organoid (PDO)-based drug screening and investigate the underlying therapeutic mechanism.

Methods

Drug screening was performed on ATC organoids using a drug library of stem cell differentiation compounds. RNA-sequencing identified pathway-level mechanisms, while structure-based molecular docking prioritized target proteins.

Results

Using a library of stem cell differentiation compounds, we identified homoharringtonine (HHT) as a potent inhibitor for ATC growth in vit

SUBMITTER: Zhang X 

PROVIDER: S-EPMC12748095 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature