| Abstract Number: | 3764 | ||||||||||||||||||||||||||||||||||||||||||||||||
| Presentation Title: | Trabectedin activity in patient-derived mesothelioma xenografts . | ||||||||||||||||||||||||||||||||||||||||||||||||
| Presentation Time: | Tuesday, Apr 19, 2016, 1:00 PM - 5:00 PM | ||||||||||||||||||||||||||||||||||||||||||||||||
| Author Block: | Simonetta Andrea Licandro1, Roberta Frapolli1, Ezia Bello1, Roberta Libener2, Sara Orecchia2, Federica Grosso2, Maurizio D'Incalci1. 1IRCCS -Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy; 2ASO SS Antonio e Biagio e C Arrigo, Alessandria, Italy | ||||||||||||||||||||||||||||||||||||||||||||||||
| Abstract Body: | Malignant pleural mesothelioma (MPM) incidence is increased over the past two decades and it is predicted to increase further in the next 20 years especially in developing countries where asbestos has not yet been banned. Surgery is not an option for the majority of patients due to the diffuse growth of MPM, making chemotherapy the treatment of choice, but prognosis remains very poor with a median survival time of 10-17 months. Trabectedin (ET-743, Yondelis) is a marine alkaloid used for the 2nd line therapy of ovarian cancer (combined with pegylated doxorubicin) and soft tissue sarcomas. It binds the DNA minor groove modulating transcription of cancer cells and has an anti-inflammatory effect modifying tumor microenvironment and reducing tumor associated macrophages. The aim was to test antitumor activity of trabectedin in newly established patient derived xenografts of MPM. MPM473, MPM484 and MPM487 xenografts were obtained in athymic nude mice by s.c. injection of 107 cells isolated from the pleural effusion of MPM patients and maintained by serial passages in mice. H&E staining and immunohistochemistry were performed. Mice were randomized when tumor reached about 200 mg to receive trabectedin, cisplatin, pemetrexed, gemcitabine, and imatinib. Antitumor activity was expressed as T/C% were T and C are the mean tumor weight of treated and control mice, respectively. The three xenografts reproduced the morphology and the histochemical profile of the human tumors. As reported in the table trabectedin was able to induce a 50% reduction in tumor growth in MPM473 and MPM 487 xenografts and only a marginal effect in MPM484 xenograft.
In conclusion we report three new MPM xenografts able to mimic the pathological features of human MPM. Although trabectedin showed only a moderate antitumor activity in our experimental models, its efficacy is comparable or better than that of the other drugs currently used for this disease. Studies are in progress in syngenic models that are more appropriate to test also the ability of trabectedin to modulate the immune system. | ||||||||||||||||||||||||||||||||||||||||||||||||