Introduction/Background Endometrial 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 clinically relevant models for EC and OC.

Methodology Mouse 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 tumoural endometrial tissues) and from the tissue implanted in mice. OC organoids were generated from malignant ascites and tumoral tissue of advanced OC patients. All models were molecularly and pathologically characterized by sequencing, immunohistochemistry and/or immunofluorescence.

Results Out of 151 tumors implanted in mice, we successfully engrafted and grew tumors derived from 36 endometrioid EC, 32 non-endometrioid EC, and 4 OC patients; being in total 72 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 tumor or patient tumor or uterine biopsies) were more successful than organoids developed from non-endometrioid histologies, i.e. 90% successful rate in endometrioid organoids generation vs. 30% in non-endometrioid. OC models were generated from 12 ascites and 2 tumor tissues with a 50% and 100% generation rate, respectively. Immunofluorescence of organoids confirmed the epithelial origin of all organoids.

Conclusion We 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.

Disclosures Authors do not have any conflict of interest.