Organoid Models Derived from Primary Tumors and Patient-Derive Xenograft Tumors Reflect Platinum Sensitivity of Ovarian Cancer Patients

Abstract

AbstractOvarian cancer (OC) remains the deadliest gynecological cancer, primarily due to late stage diagnosis and high rates of chemotherapy resistance and recurrence. Lack of representative preclinical models exacerbates the challenges of discovering effective therapies to treat platinum-resistant OC. Patient-derived xenograft (PDX) models maintain the genetic characteristics of the original tumor, but require considerable development time and have limited screening capabilities. Organoid models mimic the tumor’s 3D structure and preserve intra-tumoral heterogeneity, so are ideal for drug screening. The purpose of this study was to determine if PDX-derived organoids (PDXOs) can reflect patient responses to chemotherapy similar to organoids derived from primary patient tumors (PDOs). In drug response assays, PDXOs and PDOs demonstrated similar sensitivity to standard chemotherapy. Furthermore, both PDXOs and PDOs reliably reflected patient response based on the clinical designation of platinum sensitivity. Seven out of eight models derived from six platinum-sensitive cases showed a significant reduction in cell viability when treated with carboplatin, paclitaxel, or the combination therapy. Six of seven organoid models derived from four platinum-resistant or refractory patients demonstrated little to no reduction in cell viability with carboplatin or combination treatment. In these platinum-resistant models, response to single agent paclitaxel was mixed, suggesting that organoid models could predict response to second-line paclitaxel. This study demonstrates that PDXOs can effectively mirror patient responses to chemotherapy, underscoring their potential as valuable, renewable models for screening novel therapies and developing personalized treatment strategies in OC.