GynePDX: A new platform of preclinical models for endometrial and ovarian cancers

BackgroundEndometrial Cancer (EC) and Ovarian Cancer (OC) are two of the major gynaecological cancers worldwide. Due to cancer cell lines failing to represent the complexity of a living organism, the development of clinically relevant models is an urgent need for the improvement of therapy research. Here, we present a newly established platform of patient-dervied organoids and mouse models for EC and OC.MethodsMouse models were developed by subcutaneous implantation of tumor samples from EC and OC patients. In parallel, EC organoids were generated directly from patients (uterine biopsy, normal and tumour endometrial tissues) and from the tissue implanted in mice. OC organoids were generated from malignant ascites and tumor tissue of advanced OC patients. All models were characterized by sequencing, immunohistochemistry and/or immunofluorescence; and were used for drug screening (organoids) and preclinical studies (mouse models).ResultsOut of 155 tumors implanted in mice, we successfully engrafted and grew tumors derived from 36 endometrioid EC, 32 non-endometrioid EC, and 8 OC patients; being in total 76 patient-derived xenograft (PDX) mouse models. Characterization of PDX models showed a high pathological and molecular correlation with the patient tumor. Organoids developed from endometrioid histologies (either from mouse or patient tumor or uterine biopsies) presented a higher generation rate than organoids developed from non-endometrioid histologies, i.e. 90% successful rate in endometrioid vs. 30% in non-endometrioid. OC models were generated from 16 ascites and 4 tumor tissues with a 62,5% and 100% generation rate, respectively. Immunofluorescence confirmed the epithelial origin of all organoids. Drug screening and preclinical studies permitted to define the chemo-resistance/sensitivity of the most common standard treatment in EC and OC, i.e. Carboplatin, Olaparib, and Niraparib.ConclusionsWe have established the GynePDX platform (www.gynepdx.com), an extensive platform of gynaecological preclinical models, including mouse models and 3D cells (organoids) for EC and OC patients. GynePDX was established to advance on precision medicine for EC and OC and to bridge the gap between preclinical and clinical research for gynaecological cancers.Legal entity responsible for the studyGroup of Biomedical Research in Gynecology, Vall d’Hebron Institute of Research.FundingHas not received any funding.DisclosureAll authors have declared no conflicts of interest.