Developing Organoids from Ovarian Cancer as Experimental and Preclinical Models

Abstract

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.

Promising Applications of Tumor Spheroids and Organoids for Personalized Medicine

“…To study the phenotypic effects of CDH1 and RHOA mutations in organoids, the CRISPR-Cas9 technique was used [ 94 ]. Organoids obtained from the patient’s ovarian cancer tissue have similarities to native tissue and reproduce the cellular and molecular phenotype of the disease [ 95 , 96 ]. Interestingly, the addition of NRG1 significantly increased the number of organoids [ 95 ].…”

“…Organoids obtained from the patient’s ovarian cancer tissue have similarities to native tissue and reproduce the cellular and molecular phenotype of the disease [ 95 , 96 ]. Interestingly, the addition of NRG1 significantly increased the number of organoids [ 95 ]. Puca et al have showed genomic, transcriptome and epigenome similarities between organoids and biopsy of a prostate neuroendocrine tumor [ 86 ].…”

Organoid technology in female reproductive biomedicine

“…These organoids recapitulate histological and genomic features of the lesions from which they were derived and represent intra-and interpatient heterogeneity [15,16]. Moreover, ovarian cancer organoids display somatic mutations and amplifications/deletions [15] and recapitulated the parent tumor's marker expression and mutational landscape [16]. Moreover, the organoids showed tumor-specific sensitivity to chemotherapeutic drugs and therefore provide a reliable preclinical tools for drug screening and discovery [15,16].…”

“…Access to reliable experimental models that address clinical challenges, such as early detection, tumor recurrence, and acquired chemotherapy resistance, is a high priority in ovarian cancer research. Recently, successful generation ovarian cancer organoids was reported by two separate groups [15,16]. These organoids recapitulate histological and genomic features of the lesions from which they were derived and represent intra-and interpatient heterogeneity [15,16].…”

“…Recently, successful generation ovarian cancer organoids was reported by two separate groups [15,16]. These organoids recapitulate histological and genomic features of the lesions from which they were derived and represent intra-and interpatient heterogeneity [15,16]. Moreover, ovarian cancer organoids display somatic mutations and amplifications/deletions [15] and recapitulated the parent tumor's marker expression and mutational landscape [16].…”