L'inibitore allosteroide IDH1 ivosidenib supera la chemioresistenza nei modelli di cholangiocarcinoma intraepatico esprimenti IDH1 di tipo selvaggio.

Gemcitabine-based chemotherapy is the standard treatment regimen for advanced intrahepatic cholangiocarcinoma (iCCA), but the frequent presence of chemoresistance limits its efficacy. Here, we identified isocitrate dehydrogenase 1 (IDH1) as the crucial target that confers chemoresistance of iCCA to gemcitabine using a druggable CRISPR/Cas9 library. The positive association between IDH1 expression and chemoresistance was revealed in a gemcitabine-treated iCCA cohort and with cell-based drug sensitivity assays. Utilizing patient-derived organoids, cell line-derived xenografts, and patient-derived xenografts, we demonstrated that IDH1 knockdown or IDH1 pharmacological inhibition facilitated gem