Abstract 55: Predicting drug sensitivity in patient derived ex vivo 3D mesothelioma cultures

Abstract

Abstract Background Malignant pleural mesothelioma (MPM) is almost exclusively linked to asbestos exposure with a latency period that is usually more than 30 years. Once diagnosis is made, the prognosis is poor. Systemic treatment combines an antifolate combined with platinum, resulting in modest responses for 40% of the patients. Recently, the addition of bevacizumab to this combination has shown to be of benefit. To date it is impossible to identify the patients who will respond before start of treatment. Second line treatments (either gemcitabine or vinorelbine) have shown to be of benefit in only a small percentage of patients. Tools to improve stratification for systemic treatment in the clinic would be of great value. Our technology based on image analysis of 3D tumor cultures accommodates accurate evaluation of drug sensitivity with small amounts of heterogeneous tumor material (tumor, pleural effusion). We have initiated clinical trials to establish the value of the platform for treatment response prediction for cancer patients, including mesothelioma. Based on the results from these trials we plan to develop diagnostics to predict drug responses for cancer patients. Methods 3D mesothelioma cultures embedded in a protein-rich hydrogel are generated from pleural effusion of chemo naïve patients, and exposed to standard-of-care therapies, targeted therapies and drug combinations. An automated high content screening platform measures cell and tissue morphology, and reports responses such as tumor cell killing, growth arrest, apoptosis, and local invasion. Morphological features are per drug selected as standard read-outs for the response. We correlate clinical response on standard of care drugs with drug response of patients’ tumor cultures. Results We present first results of drug sensitivity in patient derived ex vivo 3D pleural effusion cultures. Results are generated within three weeks after the pleural fluid is obtained from the patients. Take rates are >80%. Standard-of-care therapies were tested and results are compared with clinical response. Patient specific drug responses are identified. Conclusion Ex vivo 3D mesothelioma cultures enable drug sensitivity testing in weeks. Measuring patient-specific treatment responses to standard-of-care drugs, and potential novel therapeutic approaches offer opportunities to personalize treatment for mesothelioma patients. Ongoing trials will reveal the correlation of our in vitro test with treatment responses and relevant diagnostics parameters in the clinic. Keywords: predictive test, mesothelioma, ex vivo 3D tumor cultures Citation Format: Robin Cornelissen, Daphne Dumouline, Jan vd Thusen, Sander Basten, Fanny Grillet, Kuan Yan, Leo Price, Willemijn Vader. Predicting drug sensitivity in patient derived ex vivo 3D mesothelioma cultures [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 55.