Long-term patient-derived ovarian cancer organoids closely recapitulate tumor of origin and clinical response

Abstract

There is an urgent need of precision medicine for ovarian cancer patients to identify patients who respond to chemotherapy and PARP inhibitors, a therapy targeting homologous recombination deficiency (HRD). Here we established a panel of 37 long-term patient-derived tumor organoids (PDTO) models of various histological subtypes from 224 patients and demonstrated that they mimic the histological and molecular characteristics of original tumors. Screening of chemotherapeutic drugs showed that PDTO exhibit heterogeneous responses, and that response of PDTO from high-grade serous ovarian carcinoma to carboplatin recapitulated patient response to first-line treatment. Additionally, the detection of HRD phenotype of PDTO using functional assay was associated with the results of the HRD test Genomic Instability Scar (GIScar). Although larger-scale investigations are needed to confirm the predictive potential of PDTO, these results provide further evidence of the potential interest of ovarian PDTO for functional precision medicine even if many challenges remain to be addressed.