Abstract
This study established a panel of patient-derived spheroids from ovarian cancer clinical materials to explore the chemoresistance mechanisms. A systematic evaluation using platinum-based compounds showed variable sensitivities among the spheroids. Integrative analyses combining gene expression profiling and chemoresistance data highlighted the role of glucose-6-phosphate dehydrogenase (G6PD) and glutathione-producing enzymes in conferring cisplatin resistance. Elevated G6PD levels correlated with poor prognosis and enhanced resistance, whereas treatment combining a G6PD inhibitor with cisplatin significantly reduced spheroid proliferation and peritoneal metastasis in mouse models. These findings emphasize the importance of patient-derived cells and integrated approaches in uncovering molecular bases of drug resistance in cancer.