1 Trabectedin efficacy in Ewing sarcoma is greatly increased by combination with anti-IGF 1 signaling agents 2 3 Ana Teresa Amaral 1* , Cecilia Garofalo 2* , Roberta Frapolli 3 , Maria Cristina Manara 2 , 4 Caterina Mancarella 2 , Sarah Uboldi 3 , Silvana Di Giandomenico 3 , Jose Luis Ordóñez 1 , 5 Victoria Sevillano 1 , Roberta Malaguarnera 4 , Piero Picci 2 , A. Bass Hassan 5 , Enrique De 6 Alava 1 , Maurizio D’Incalci 3 , and Katia Scotlandi 2 . 7 1 Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del 8 Rocio/CSIC/Universidad de Sevilla, Dept. of Pathology. 41013 Seville, Spain.; 2 CRS Development 9 of Biomolecular Therapies, Experimental Oncology Lab, Rizzoli Institute, Bologna, Italy; 3 10 Department of Oncology IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy; 4 11 Department of Health, University of Catanzaro, Catanzaro, Italy; 5 Sir William Dunn School of 12 Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE 13 *Ana Teresa Amaral and Cecilia Garofalo are the first authors and contributed equally to 14 this work. 15 16 Running title: Trabectedin affects IGF1R and synergizes with anti-IGF1R drug 17 Key words: Trabectedin, Insulin like growth factor, Ewing sarcoma, DNA damage, EWS-FLI1 18 Financial Support: This work was financially supported by the EU project FP7-HEALTH-2011- 19 two-stage, Project ID 278742 EUROSARC; the Italian Association for Cancer Research (Katia 20 Scotlandi - AIRC Project N.14049; Cecilia Garofalo -MFAG N.11584 and Maurizio D'Incalci - 21 AIRC Project N.14658); The Italian Ministry of Research and Education (F.I.R.B. project 22 number:RBAP11884M_005); The Italian Ministry of the Health (67/GR-2010-2319511, CUP 23 Research. on June 4, 2016. © 2015 American Association for Cancer clincancerres.aacrjournals.org Downloaded from Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on January 21, 2015; DOI: 10.1158/1078-0432.CCR-14-1688