Organoid models in gynaecological oncology research

Abstract

Cell culture and animal models represent experimental cornerstones for the investigation of tissue, organ and body physiology in the context of gynaecological research. However, their ability to accurately reflect human mechanisms in vivo is limited. The development of organoid technologies has begun to address this limitation by providing platforms ex vivo that resemble the phenotype and genotype of the multi-cellular tissue from which they were derived more accurately. In this review, we discuss advances in organoid derivation from endometrial, ovarian, fallopian tube and cervical tissue, both benign and malignant, the manipulation of organoid microenvironment to preserve stem cell populations and achieve long-term expansion and we explore the morphological and molecular kinship of organoids to parent tissue. Apart from providing new insight into mechanisms of carcinogenesis, gynaecological cancer-derived organoids can be utilised as tools for drug screening of chemotherapeutic and hormonal compounds where they exhibit interpatient variability consistent with states in vivo and xenografted tumours allowing for patient-tailored treatment strategies. Bridging organoid with bioengineering accomplishments is clearly the way forward to the generation of organoid-on-a-chip technologies enhancing the robustness of the model and its translational potential. Undeniably, organoids are expected to stand their ground in the years to come and revolutionize development and disease modelling studies.