Ex vivo 3D micro-tumour testing platform for predicting clinical response to platinum-based therapy in patients with high-grade serous ovarian cancer

  • NPJ Precis Oncol. 2025 Aug 30;9(1):306. doi: 10.1038/s41698-025-01080-8.
Esmee Koedoot  #  1 ,  Dieudonné J van der Meer  #  2 ,  Anne M van Altena  3 ,  Lieke J Ceton  2 ,  Timothy J P Sijsenaar  2 ,  Marta G Montero  2  4 ,  Fanny Grillet  2 ,  Jurgen M J Piek  5 ,  Ruud L M Bekkers  3  5  6 ,  Maurice J D L van der Vorst  7 ,  Auke M T Huijben  8 ,  Astrid Baalbergen  9 ,  Kevin G J A Voogdt  10 ,  Loes Verhoeven  11 ,  Huberdina P M Smedts  12 ,  Klaus Weber  13 ,  Hans Marten Hazelbag  14 ,  Tjalling Bosse  15 ,  Els L van Persijn-van Meerten  16 ,  Cornelis D de Kroon  17 ,  Leo Price  18 ,  Willemijn Vader  2 ,  Judith R Kroep  19 ,  Nelleke P B Ottevanger  20
Affiliations
  • 1. VitroScan, Leiden, The Netherlands. [email protected].
  • 2. VitroScan, Leiden, The Netherlands.
  • 3. Radboud University Medical Center, Gynaecologische Oncology, Nijmegen, The Netherlands.
  • 4. Bristol Myers Squibb, Oegstgeest, The Netherlands.
  • 5. Catharina Ziekenhuis, Gynaecology, Eindhoven, The Netherlands.
  • 6. GROW, School for Oncology and Reproduction, Maastricht University, Maastricht, The Netherlands.
  • 7. Rijnstate, Interne Geneeskunde, Arnhem, The Netherlands.
  • 8. Maasstad Ziekenhuis, Interne Geneeskunde, Rotterdam, The Netherlands.
  • 9. Reinier de Graaf Ziekenhuis, Gynaecology, Den Haag, The Netherlands.
  • 10. Haga Ziekenhuis, Gynaecology, Den Haag, The Netherlands.
  • 11. Laurentius Ziekenhuis, Roermond, The Netherlands.
  • 12. Amphia Ziekenhuis, Gynaecology, Breda, The Netherlands.
  • 13. Anapath, Basel, Switzerland.
  • 14. HMC Haaglanden, Pathology, Den Haag, The Netherlands.
  • 15. Leiden University Medical Center, Pathology, Leiden, The Netherlands.
  • 16. Leiden University Medical Center, Radiology, Leiden, The Netherlands.
  • 17. Leiden University Medical Center, Gynaecology, Leiden, The Netherlands.
  • 18. Crown Bioscience, Leiden, The Netherlands.
  • 19. Leiden University Medical Center, Medical Oncology, Leiden, The Netherlands.
  • 20. Radboud University Medical Center, Medical BioSciences, Nijmegen, The Netherlands.
  • # Contributed equally.
PMID: 40885787 DOI: 10.1038/s41698-025-01080-8
Abstract

Around 20% of patients with primary high-grade ovarian Cancer do not respond to chemotherapy, but predictive biomarkers are lacking. The purpose of the current study is to establish and clinically validate an ex vivo 3D micro-tumour testing platform that predicts patient-specific response to standard of care chemotherapy. 104 ovarian Cancer patients with malignant ascites were included in the study. Micro-tumours enriched from ascites were exposed to standard of care chemo- and targeted therapies, imaged using a high-content 3D screening platform. Morphological features were extracted for sensitivity profiling. A linear regression model was trained to predict the patient's CA125 decay rates, which were correlated to clinical outcomes (patient CA125 decay rate, change in tumour size, and progression-free survival). Isolated micro-tumours recapitulated ovarian Cancer markers. A significant correlation (R = 0.77) between predicted and clinical CA125 rates was observed. Patients with predicted high ex vivo sensitivity to carboplatin/paclitaxel demonstrated significantly increased PFS and decreased tumour size. Complementary, patient-specific response profiles for second-line therapies were calculated and presented in integrated reports. In conclusion, an ex vivo 3D micro-tumour testing platform was established that predicted clinical response to neo-adjuvant chemotherapy in ovarian Cancer patients and measured patient-specific responses to second-line therapies as a proof-of-concept. The platform enabled stratification of responders vs non-responders and has the potential to support informed treatment decisions after prospective validation. Results are generated within 2 weeks after sample collection, aligning with the clinical time frame for treatment decision-making.

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