Ex vivo 3D micro-tumour testing platform for predicting clinical response to platinum-based therapy in patients with high-grade serous ovarian cancer
Year: 2025
Type: article
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.
Source: npj Precision Oncology
Authors: Esmee Koedoot, Dieudonné J. van der Meer, Anne M. van Altena, Lieke J. Ceton, Timothy J. P. Sijsenaar, Marta G. Montero, Fanny Grillet, Jurgen M. J. Piek, Ruud L. M. Bekkers, Maurice J. D. L. van der Vorst, Auke M. T. Huijben, Astrid Baalbergen, Kevin G. J. A. Voogdt, Loes Verhoeven, Huberdina P. M. Smedts, Klaus Weber, Hans Marten Hazelbag, Tjalling Bosse, Els L. van Persijn-van Meerten, Cornelis D. de Kroon, Leo Price, Willemijn Vader, Judith R. Kroep, Nelleke P. B. Ottevanger
Institutions: Radboud University Medical Center, Bristol-Myers Squibb (Netherlands), Catharina Ziekenhuis, Maastricht University, Rijnstate Hospital, Maasstad Ziekenhuis, Haga Hospital, Laurentius Ziekenhuis, Amphia Ziekenhuis, Medisch Centrum Haaglanden, Stichting Haaglanden Medisch Centrum, Leiden University Medical Center, Radboud University Nijmegen
Language: English
Subfield: Reproductive Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,090
OpenAlex ID: W4413843980