LAUSR

Introduction: Comprehensive profiling of tumors using omics technologies has improved our understanding of the molecular landscape of endometrial cancer (EC), building the foundation for precision medicine. However, targeted therapies that show promise in preclinical research are failing clinical trials, which is partly explained by the lack of models that mimic the physiopathology of patients. We aimed at establishing organoids and organoid-based patient-derived xenograft (O-PDX) models as part of a new preclinical platform for endometrial cancer. Methods: Aggregates of tumor cells were isolated from fresh tumor samples, followed by long-term culturing as organoids in a chemically defined medium. Established organoids were implanted into the left uterine horn of NSG mice, and tumor growth was monitored using near-infrared fluorescence imaging (NIRF). Patient tissue, organoids, and corresponding O-PDXs were characterized by histology and whole-exome sequencing and by immunohistochemical staining of important endometrial cancer biomarkers. For proof of concept, selected models were treated with conventional therapeutic agents, including in vivo treatment with carboplatin. Results: Organoids and orthotopic O-PDXs representing different subtypes of endometrial cancer were successfully established. Histologic and molecular profiles of organoids are similar to patient tissue, also after long-term culturing, and characteristics of O-PDXs were sustained after rederivation in vivo. Proof-of-concept drug testing shows heterogenous sensitivity to clinically administered chemotherapeutics. Conclusion: We have extended the collection of EC organoids and established O-PDX models for in vivo studies. This state-of-the-art preclinical platform enables more clinically relevant drug testing that will facilitate translation into relevant clinical trials. Citation Format: Hege F. Berg, Tina Fonnes, Elin Strand, Heidi Espedal, Ingunn M. Stefansson, Emmet McCormack, Line Bjorge, Jone Trovik, Ingfrid S. Haldorsen, Erling A. Hoyvik, Camilla Krakstad. Patient-derived organoid-based models for endometrial cancer [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr A16.