Developing Organoids from Ovarian Cancer as Experimental and Preclinical Models
Ovarian cancer (OC) represents the most dismal gynecological cancer. Pathobiology is poorly understood, mainly due to lack of appropriate study models. Organoids, defined as self-developing three-dimensional in vitro reconstructions of tissues, provide powerful tools to model human diseases. Here, we established organoid cultures from patient-derived OC, in particular from the most prevalent high-grade serous OC (HGSOC). Testing multiple culture medium components identified neuregulin-1 (NRG1) as key factor in maximizing OC organoid development and growth, although overall derivation efficiency remained moderate (36% for HGSOC patients, 44% for all patients together). Established organoid lines showed patient tumor-dependent morphology and disease characteristics, and recapitulated the parent tumor's marker expression and mutational landscape. Moreover, the organoids displayed tumor-specific sensitivity to clinical HGSOC chemotherapeutic drugs. Patient-derived OC organoids provide powerful tools for the study of the cancer's pathobiology (such as importance of the NRG1/ERBB pathway) as well as advanced preclinical tools for (personalized) drug screening and discovery. ; We thank the UZ/KU Leuven Genomics Core for their expert assistance in array CGH analysis, and Thomas Van Brussel (D.L.'s group) for technical help in genome sequencing. We are grateful to Lara Vankelecom (University of Ghent, Faculty of Psychology and Educational Sciences, Department of Data Analysis) for expert help with statistical analyses. The computational resources and services used for genome sequencing and analysis were provided by the Flemish Supercomputer Center (VSC), funded by the Hercules Foundation and the Flemish Government, Department of Economy, Science and Innovation (EWI). We are also grateful to InfraMouse (VIB-KU Leuven, Hercules type 3 project ZW09-03) for use of histological instruments and microscopes. This work was supported by grants from the KU Leuven Research Fund and from the Fund for Scientific Research (FWO) - Flanders (Belgium). N.M. is, and B.C. was, a PhD Fellow of the FWO. D.T. is a Senior Clinical Investigator of the FWO.
