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Title: | Sunitinib inhibits tumor growth and synergizes with cisplatin in orthotopic models of cisplatin-sensitive and cisplatin-resistant human testicular germ cell tumors |
Author: | Castillo-Ávila, Wilmar Piulats, Josep M. García del Muro Solans, Xavier Vidal-Bel, August Condom i Mundó, Enric Casanovas i Casanovas, Oriol Mora, Josefina Germà Lluch, José Ramón Capellá, G. (Gabriel) Villanueva Garatachea, Alberto Viñals Canals, Francesc |
Keywords: | Medicaments antineoplàstics Cisplatí Quimioteràpia del càncer Malalties del testicle Tumors Càncer Antineoplastic agents Cisplatin Cancer chemotherapy Testis diseases Tumors Cancer |
Issue Date: | 15-May-2009 |
Publisher: | American Association for Cancer Research |
Abstract: | Purpose: germ cell tumors (GCT) of the testis are highly curable, but those patients who are refractory to cisplatin (CDDP)-based combination chemotherapy have a poor prognosis. Therefore, identifying new alternatives for treatment remains a priority. Several studies support an important role for angiogenesis in GCTs, suggesting that antiangiogenic treatment might be a good alternative. Sunitinib is an oral multitarget tyrosine kinase receptor inhibitor with antiangiogenic and antitumor activities. In the present study, we evaluated the effect of sunitinib, CDDP, or the combination of both drugs using an orthotopic model of human testicular GCT. Experimental design: mice were implanted with four different testicular tumors: a yolk sac, two choriocarcinomas, and a CDDP-resistant choriocarcinoma variant induced in mice by continuous exposure to CDDP. Mice were treated with vehicle, CDDP, sunitinib, or the combination of both drugs and their effects on tumors were analyzed. Results: we observed a significant inhibition in tumor growth accompanied by longer survival after sunitinib treatment. Combination therapy with CDDP significantly enhanced these effects. Sunitinib induced apoptosis, reduced tumor cell proliferation and tumor vasculature, and inhibited vascular endothelial growth factor receptor 1, 2, and 3 and platelet-derived growth factor receptor α phosphorylation without affecting phosphorylation of other tyrosine kinase receptors. More importantly, tumor growth inhibition induced by sunitinib was also observed in the induced CDDP-resistant choriocarcinoma model. Conclusions: taken together, these results suggest that sunitinib might be a new alternative for treatment of CDDP-refractory patients. |
Note: | Versió postprint del document publicat a: https://doi.org/10.1158/1078-0432.CCR-08-2170 |
It is part of: | Clinical Cancer Research, 2009, vol. 15, num. 10, p. 3384-3395 |
URI: | http://hdl.handle.net/2445/120402 |
Related resource: | https://doi.org/10.1158/1078-0432.CCR-08-2170 |
ISSN: | 1078-0432 |
Appears in Collections: | Articles publicats en revistes (Ciències Fisiològiques) Articles publicats en revistes (Ciències Clíniques) Articles publicats en revistes (Patologia i Terapèutica Experimental) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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