Systematic screening identifies dual PI 3 K and mTOR inhibition as a conserved 2 therapeutic vulnerability in osteosarcoma 3 4

1 Systematic screening identifies dual PI3K and mTOR inhibition as a conserved 2 therapeutic vulnerability in osteosarcoma 3 4 Ankita Gupte, Emma K Baker, Soo-San Wan, Elizabeth Stewart, Amos Loh, Anang 5 A. Shelat, Cathryn M. Gould, Alistair M Chalk, Scott Taylor, Kurt Lackovic, Åsa 6 Karlström, Anthony J Mutsaers, Jayesh Desai, Piyush B Madhamshettiwar, Andrew CW 7 Zannettino, Chris Burns, David CS Huang, Michael A Dyer, Kaylene J 8 Simpson & Carl R Walkley 9 10 St. Vincent’s Institute of Medical Research and Department of Medicine, St Vincent’s 11 Hospital, University of Melbourne, Fitzroy, VIC 3065, Australia; 12 The Walter and Eliza Hall Institute of Medical Research and Department of Medical Biology, 13 University of Melbourne, Parkville, VIC 3052, Australia; 14 Department of Developmental Neurobiology, St. Jude Children’s Research Hospital, 15 Memphis, TN 38105, USA; 16 Department of Chemical Biology and Therapeutics, St. Jude Children’s Research Hospital, 17 Memphis, TN 38105, USA; 18 Victorian Centre for Functional Genomics, Peter MacCallum Cancer Centre, East Melbourne, 19 VIC 3002, Australia; 20 Ontario Veterinary College, University of Guelph, Guelph, Ontario N1G 2W1 Canada. 21 Department of Medical Oncology, Royal Melbourne Hospital and Peter MacCallum Cancer 22 Centre, Melbourne, VIC 3002, Australia 23 Myeloma Research Laboratory, School of Medical Sciences, Faculty of Health Sciences, 24 University of Adelaide, Adelaide, SA 5005, Australia and Cancer Theme, South Australian 25 Health and Medical Research Institute, Adelaide, SA 5000, Australia; 26 Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; 27 Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC 28 3052, Australia 29