Journal of translational medicine · 2026
Patient-derived organoids predict responses to chemotherapy and PARP inhibitors in advanced ovarian cancer.
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Wang Haixia, Wang Ling, Zhu Xueping, He Misi, Zhong Lin, Lv Yuyu, Li Qiaoling, Jiang Qinyue, Zhang Cong, Liu Xinghe, Zou Dongling
Аннотация
BACKGROUND: While tumor organoids hold promise for personalized medicine, clinical validation of epithelial ovarian cancer (EOC) organoids as predictors of therapeutic efficacy-particularly for PARP inhibitors (PARPi)-remains unestablished.
METHODS: Patient-derived organoids (PDOs) were established from treatment-naive EOC specimens and characterized by H&E staining, immunohistochemistry, and whole-exome sequencing. Drug sensitivity testing (DST) was performed using carboplatin, paclitaxel, and PARPi (olaparib and niraparib). Clinical homologous recombination deficiency (HRD) status was assessed by tumor sequencing. Organoid responses were prospectively compared to patient outcomes after first-line chemotherapy (carboplatin/paclitaxel) and PARPi maintenance.
RESULTS: PDOs were successfully established from 21 of 30 patients (70%) across multiple EOC subtypes and preserved the histopathological features and genomic landscapes of their corresponding primary tumors. Organoid-based DST accurately predicted responses to first-line carboplatin/paclitaxel, with a sensitivity of 100% (95% CI 62.88-100%), specificity of 66.67% (95% CI 12.53-98.23%), accuracy of 91.67% (95% CI 61.52-99.79%), AUC of 0.95 (95% CI 0.85-1.00), and Cohen's kappa of 0.75 (95% CI 0.30-1.00). In evaluating PARPi response, organoids revealed discrepancies between genomic HRD status and actual drug responses. One HRD-positive PDO was PARPi-resistant, consistent with patient non-response, while two HRR-proficient PDOs showed PARPi sensitivity and corresponding clinical benefit.
CONCLUSIONS: EOC-derived PDOs provide a robust platform for predicting chemotherapy response and offer added value in assessing PARPi efficacy beyond genomic profiling. Combination of organoid-based testing with genomic analysis may improve precision treatment strategies in EOC.
METHODS: Patient-derived organoids (PDOs) were established from treatment-naive EOC specimens and characterized by H&E staining, immunohistochemistry, and whole-exome sequencing. Drug sensitivity testing (DST) was performed using carboplatin, paclitaxel, and PARPi (olaparib and niraparib). Clinical homologous recombination deficiency (HRD) status was assessed by tumor sequencing. Organoid responses were prospectively compared to patient outcomes after first-line chemotherapy (carboplatin/paclitaxel) and PARPi maintenance.
RESULTS: PDOs were successfully established from 21 of 30 patients (70%) across multiple EOC subtypes and preserved the histopathological features and genomic landscapes of their corresponding primary tumors. Organoid-based DST accurately predicted responses to first-line carboplatin/paclitaxel, with a sensitivity of 100% (95% CI 62.88-100%), specificity of 66.67% (95% CI 12.53-98.23%), accuracy of 91.67% (95% CI 61.52-99.79%), AUC of 0.95 (95% CI 0.85-1.00), and Cohen's kappa of 0.75 (95% CI 0.30-1.00). In evaluating PARPi response, organoids revealed discrepancies between genomic HRD status and actual drug responses. One HRD-positive PDO was PARPi-resistant, consistent with patient non-response, while two HRR-proficient PDOs showed PARPi sensitivity and corresponding clinical benefit.
CONCLUSIONS: EOC-derived PDOs provide a robust platform for predicting chemotherapy response and offer added value in assessing PARPi efficacy beyond genomic profiling. Combination of organoid-based testing with genomic analysis may improve precision treatment strategies in EOC.