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. •Organoids are established from ovarian cancer (OC)•Neuregulin-1 (NRG1) is identified as key component for OC organoid growth•OC organoids capture disease hallmarks and recapitulate patient tumor characteristics•OC organoids are amenable to drug screening and mechanistic (NRG1/ERBB) research In this article, Vankelecom and colleagues developed a well-defined protocol to establish organoid cultures from ovarian cancer (OC), particularly from the prevalent high-grade serous OC. The organoids capture disease hallmarks and patient tumor characteristics and provide powerful experimental models to decipher the cancer's pathobiology (such as the role of NRG1/ERBB), as well as preclinical tools for (personalized) drug screening and discovery.