Patient-derived organoids in gynaecological cancers: emerging tools for therapy and disease modelling

Patient-derived organoids (PDOs) have emerged as physiologically relevant three-dimensional (3D) culture systems that closely mimic the molecular and histological features of the human endometrium and associated malignancies. Owing to their complex pathophysiology and limited treatment options, gynaecological cancers and benign disorders such as endometriosis and adenomyosis continue to pose serious challenges to women's health. This review highlights how PDO technology is changing the face of modelling gynaecological diseases, testing responses to drugs, and preparing personalised treatment, focussing on the mechanistic aspects of tumour evolution, hormone responsiveness, and chemoresistance, and the recent developments in PDO-based disease modelling in ovarian, endometrial, and endometriosis-related cancers. The predictive capability and translational value of PDO systems can be further improved by incorporating organ-on-a-chip platforms, CRISPR/Cas9 genome editing, and multiomics profiling. These biobanking programmes and microfluidic advances will permit longitudinal analyses as well as high-throughput screenings for targeted therapies against inhibitors of PARP, PI3K-AKT, and hormonal pathways. Although several technical challenges, such as low sample heterogeneity, a lack of stromal-epithelial interactions, and financial burdens, exist, PDOs have emerged as promising platforms for precision oncology, fertility preservation, and regenerative medicine research. In summary, this review presents the ability of PDO models to bridge the gap between preclinical research and clinical translation and potentially revolutionise personalised gynaecological medicine.