Targeting the Unwindosome by Mebendazole Is a Vulnerability of Chemoresistant Hepatoblastoma.

ABSTRACT: Resistance to conventional chemotherapy remains a huge challenge in the clinical management of hepatoblastoma, the most common liver tumor in childhood. By integrating the gene expression data of hepatoblastoma patients into the perturbation prediction tool Connectivity Map, we identified the clinical widely used anthelmintic mebendazole as a drug to circumvent chemoresistance in permanent and patient-derived xenograft cell lines that are resistant to cisplatin, the therapeutic backbone of hepatoblastoma treatment. Viability assays clearly indicated a potent reduction of tumor cell growth upon mebendazole treatment in a dose-dependent manner. The combination of mebendazole and cisplatin revealed a strong synergistic effect, which was comparable to the one seen with cisplatin and doxorubici

SUBMITTER: Li Q 

PROVIDER: S-EPMC9454988 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature