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

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Abstract

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.
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Abstract

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. Similar content being viewed by others Data Availability All data supporting the findings of this study are available within the paper.

References

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Acknowledgements

We sincerely thank the Sathyabama Institute of Science and Technology, Chennai, for providing valuable infrastructure and resources. Funding No specific funding/grant was received. Author information Authors and Affiliations Contributions Naveen Vigneshwaran and T. Thangam contributed equally to this work. Naveen Vigneshwaran: Conceptualization, literature review, writing-original draft preparation. T. Thangam: Literature review, manuscript development, critical revision, response to reviewer comments, table revision, and final manuscript preparation. Krupakar Parthasarathy: Supervision, critical evaluation of the manuscript, intellectual input, and final approval of the manuscript. V. Haribalaji: Figure conceptualization, manuscript review, and intellectual contribution. All authors read and approved the final manuscript. Corresponding author Ethics declarations Conflict of interest The authors declare that they have no conflicts of interest. Ethics approval The present study needs no approval or a statement of local ethics. Informed consent Not applicable Additional information Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. About this article Cite this article Vigneshwaran, N., Thangam, T., Parthasarathy, K. et al. Patient-derived organoids in gynaecological cancers: emerging tools for therapy and disease modelling. Clin Transl Oncol (2026). https://doi.org/10.1007/s12094-026-04458-7 Received: Accepted: Published: Version of record: DOI: https://doi.org/10.1007/s12094-026-04458-7

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