Objective Background/Main objective: Neuroblastoma, a solid tumor of the childhood, is the cause of 15% of deaths by cancer in children under the age of 15. Survival of advanced stage neuroblastoma patients remains poor (around 30%), because these tumors rapidly develop resistance to conventional treatments. The poor penetration of chemotherapy agents to the target tumor cells is considered one of the main mechanisms of drug resistance in solid malignancies. Therefore, the main objective of this project is to design pharmacological treatments that circumvent some of the resistance mechanisms and penetrate more efficiently to the neuroblastoma tumor cells.Methodology: We hypothesize that the penetration and activity of the genotoxic drug SN-38 in neuroblastoma tumor xenografts will be improved by its formulation as micelles and by the administration of concomitant nutlin and vandetanib (two new drugs with remarkable anti-neuroblastoma effect). To address this hypothesis, we will prepare SN-38 micelles by the self-assembly of amphiphilic polymers in water. To evaluate the penetration of SN-38 micelles to neuroblastoma xenografts, we will apply a microdialysis technique to sample the extracellular fluid of the tumors and we will analyze drug concentrations in the dialyzates. We will evaluate the effect of nutlin and vandetanib on the tumor penetration and activity of SN-38. Finally, we will test the efficacy of our treatments in a neuroblastoma tumor model and will correlate drug concentrations in plasma and tumor with the observed antineoplastic activity.Expected results: We will identify more effective therapies than the currently available for the treatment of neuroblastoma. We expect that our research will be able to rapidly be translated to the clinic and help rationally design clinical trials for the multidrug resistant neuroblastoma. Fields of science natural scienceschemical sciencespolymer sciencesmedical and health sciencesclinical medicineoncologymedical and health sciencesbasic medicinepharmacology and pharmacydrug resistancemultidrug resistance Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) FP7-PEOPLE-2009-RG - Marie Curie Action: "Reintegration Grants" Call for proposal FP7-PEOPLE-2010-RG See other projects for this call Funding Scheme MC-IRG - International Re-integration Grants (IRG) Coordinator FUNDACIO PRIVADA PER A LA RECERCA I LA DOCENCIA SANT JOAN DE DEU EU contribution € 100 000,00 Address SANTA ROSA 39-4 08950 Esplugues De Llobregat Spain See on map Region Este Cataluña Barcelona Activity type Research Organisations Administrative Contact Emili Bargalló Angerri (Mr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
