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

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

Affiliations

  • 1 VitroScan, Leiden, The Netherlands. esmee.koedoot@vitroscan.nl.
  • 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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