Objective Development of efficient therapeutic strategies in the past years has drastically reduced the lethality of several common types of pediatric and juvenile form of cancer such as leukemia, lymphoma and brain tumors. Such a tremendous success, however, does not include sarcomas treatment, whose mortality rate remains the same as twenty years ago. Ewing sarcoma is a childhood cancer with a relatively low incidence, with 3 cases/million/year. The initial oncogenic event is represented by a balanced chromosomal translocation originating a transcription factor chimeric onco-protein. Notably, 90% of Ewing sarcoma patients are characterized by the fusion between EWS and FLI1 genes. From a therapeutic point of view, as exclusive hallmark of tumor cells and driving force of the disease, the onco-chimera protein represents an ideal target, even though transcription factor onco-proteins are classified as “undruggable” from a conventional pharmacological point of view, lacking in their structure convenient targeting pockets. This project aims to break this dogma through the following steps: 1. Generation of an in vivo genetic platform based on an innovative ex vivo-in vitro-in vivo approach that will allow us to accurately recapitulate in mice Ewing sarcomagenesis; 2. Characterization in vivo and in vitro of those mechanisms and pathways that are essential for the tumorigenic process; and finally, 3. Identification of druggable targets whose fine-tuning will tear down Ewing sarcoma lethality by promoting onco-chimera degradation. The success of this project will not only lead to the development of new therapies against Ewing sarcoma, but also to the development of a novel platform which will be easily exported to other tumors driven by “undruggable” onco-chimeras. Fields of science natural sciencesbiological sciencesgeneticsgenomesviral genomesmedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesclinical medicinecardiologycardiovascular diseasesmedical and health sciencesclinical medicineoncologyleukemianatural sciencesbiological sciencesmolecular biology Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2016 - Individual Fellowships Call for proposal H2020-MSCA-IF-2016 See other projects for this call Funding Scheme MSCA-IF-EF-CAR - CAR – Career Restart panel Coordinator UNIVERSITA DEGLI STUDI DI TRENTO Net EU contribution € 180 277,20 Address Via calepina 14 38122 Trento Italy See on map Region Nord-Est Provincia Autonoma di Trento Trento Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00
