Related Experiment Video
Updated: Jul 30, 2025
Ovarian Cancer Patient-Derived Organoid Models for Pre-Clinical Drug Testing
Published on: September 15, 2023
Extraordinary clinical response to ibrutinib in low-grade ovarian cancer guided by organoid drug testing
Heidi J Gray1, Payel Chatterjee2, Rachele Rosati2
1Division of Gynecology Oncology, University of Washington, Seattle, WA, USA.
Abstract:
Low-grade serous ovarian cancer (LGSOC) typically responds poorly to standard platinum-based chemotherapy and new therapeutic approaches are needed. We describe a remarkable response to targeted therapy in a patient with platinum-resistant, advanced LGSOC who had failed standard-of-care chemotherapy and two surgeries. The patient was in rapid decline and entering hospice care on home intravenous (i.v.) opioid analgesics and a malignant bowel obstruction requiring a G-tube. Genomic analysis of the patient's tumor did not indicate obvious therapeutic options. In contrast, a CLIA-certified drug sensitivity assay of an organoid culture derived from the patient's tumor identified several therapeutic choices, including Bruton's tyrosine kinase (BTK) inhibitor ibrutinib, as well as the EGFR inhibitors afatinib and erlotinib. Following off-label administration of daily ibrutinib as monotherapy, the patient had an exceptional clinical turnaround over the following 65 weeks with normalization of CA-125 levels, resolution of the malignant bowel obstruction, halting of pain medications, and improvement of performance status from ECOG 3 to ECOG 1. After 65 weeks of stable disease, the patient's CA-125 levels began to rise, at which point the patient discontinued ibrutinib and began taking afatinib as monotherapy. The patient's CA-125 levels remained stable for an additional 38 weeks but due to anemia and rising CA-125 levels, the patient switched to erlotinib and is currently being monitored. This case highlights the clinical utility of ex vivo drug testing of patient-derived tumor organoids as a new functional precision medicine approach to identify effective personalized therapies for patients who have failed standard-of-care treatments.
Insights
Tumor organoid drug sensitivity testing identified targeted therapies for a patient with advanced, platinum-resistant low-grade serous ovarian cancer (LGSOC). This functional precision medicine approach led to a significant clinical turnaround and prolonged stable disease.
Area of Science:
- Oncology
- Genomics
- Precision Medicine
Background:
- Low-grade serous ovarian cancer (LGSOC) exhibits poor response to conventional platinum-based chemotherapy.
- Advanced LGSOC often presents resistance to standard treatments, necessitating novel therapeutic strategies.
- The case involves a patient with platinum-resistant, advanced LGSOC who had exhausted standard care options.
Purpose of the Study:
- To describe a patient with advanced LGSOC who experienced a significant clinical response to targeted therapy.
- To highlight the utility of ex vivo drug sensitivity testing using patient-derived tumor organoids.
- To demonstrate a functional precision medicine approach for identifying personalized therapies in refractory cancers.
Main Methods:
- Genomic analysis of the patient's tumor was performed.
- A CLIA-certified drug sensitivity assay was conducted on a patient-derived tumor organoid.
- The patient received off-label targeted therapies including ibrutinib, afatinib, and erlotinib based on assay results.
Main Results:
- Genomic analysis did not reveal clear therapeutic targets.
- The organoid drug sensitivity assay identified ibrutinib, afatinib, and erlotinib as potential treatments.
- Ibrutinib monotherapy resulted in a 65-week clinical turnaround, including resolution of malignant bowel obstruction and normalization of CA-125 levels.
- Subsequent treatment with afatinib and erlotinib provided additional disease stabilization.
Conclusions:
- Ex vivo drug testing of patient-derived tumor organoids can identify effective personalized therapies for LGSOC.
- Functional precision medicine approaches, like organoid drug sensitivity assays, offer viable options for patients with refractory cancers.
- This case underscores the potential of targeted therapies and novel drug testing platforms in managing advanced LGSOC.
