The ALK / ROS 1 inhibitor PF-06463922 overcomes primary 1 resistance to crizotinib in ALK-driven neuroblastoma 2 3

The ALK/ROS1 inhibitor PF-06463922 overcomes primary 1 resistance to crizotinib in ALK-driven neuroblastoma 2 3 Nicole R. Infarinato, Jin H. Park, Kateryna Krytska, Hannah T. Ryles, Renata 4 Sano, Katherine M. Szigety, Yimei Li, Helen Y. Zou, Nathan V. Lee, Tod Smeal, 5 Mark A. Lemmon, and Yael P. Mossé*. 6 7 Division of Oncology and Center for Childhood Cancer Research, The Children's Hospital of 8 Philadelphia, Philadelphia, PA, 19104, USA 9 Graduate Group in Biochemistry and Molecular Biophysics 10 Department of Biochemistry and Biophysics 11 Department of Biostatistics & Epidemiology 12 Department of Pediatrics 13 Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104 USA 14 Oncology Research Unit, Pfizer Worldwide Research and Development, San Diego, CA, 15 92121, USA 16 Present address: Department of Pharmacology and Cancer Biology Institute, Yale University, 17 New Haven, CT 06520, USA 18 19 Note: 20 Supplementary data for this article are available at Cancer Discovery 21 Online (http://cancerdiscovery.aacrjournals.org/). 22 23 N. R. Infarinato and J.H. Park contributed equally to this work 24 25 M. A. Lemmon and Y. P. Mossé jointly directed this work. 26 27 Conflict of interest disclosure statement: No conflicts of interest disclosed for NRF, JHP, KK, 28 HTR, RS, KS, MAL and YPM. HYZ, NVL and TS are employees at Pfizer, Inc. 29 30 *Corresponding Author: 31 Yael P Mossé, M.D. 32 Children's Hospital of Philadelphia 33 Division of Oncology 34 3501 Civic Center Boulevard 35 CTRB 3056 36 Philadelphia, PA 19104 37 Tel: 215-590-0965 38 Fax: 267-426-0685 39 Email: mosse@chop.edu 40 41 Running Title: ALK inhibition by PF-06463922 in neuroblastoma 42