Method Profile
Compare idarubicin sensitivity in paired liver cultures and examine its association with TACE outcomes.
Exploratory drug-response and clinical-association assessment for liver-directed idarubicin treatment.
Biopsy-derived HCC and adjacent nontumor liver organoids from the single-center TACTida trial: 17 tumor and 25 nontumor cultures were established.
Six-day organoid growth followed by 24-hour idarubicin exposure. Doxorubicin, cell-death, expression and secretion measurements were separate follow-up experiments.
Biological models
65 biopsies yielded 42 cultures. Tumor organoids were obtained for 15 of 28 patients and nontumor organoids for 20 of 28.
Drug-response readouts
Idarubicin 0–100 μM with CellTiter-Glo 3D ATP measurement; doxorubicin 0–500 μM. Live/dead, qPCR and AFP/TGF-β1 ELISA were separate assays.
Fit dose-response curves separately for tumor and nontumor cultures; compare matched culture sensitivity and test tumor IC50 against post-TACE response variables.
Paired tumor/nontumor pharmacology and exploratory clinical association.
17 paired culture comparisons. The Results describe a doxorubicin comparison for 8 patients; qPCR used 7 patients and secretion analysis used 6.
Nontumor liver organoids; doxorubicin; untreated organoids; clinical necrosis and mRECIST outcomes.
Idarubicin sensitivity varied widely. Tumor cultures were more sensitive in 7 comparisons, nontumor cultures in 7 and comparable in 3. Tumor IC50 was not significantly associated with TACE response.
Paired tumor and nontumor liver organoids showed broad variation in idarubicin sensitivity. In this small clinical cohort, tumor-organoid IC50 did not significantly correlate with necrosis or radiological response after idarubicin-based chemoembolization.
