Journal article

Systematic Screening Identifies Dual PI3K and mTOR Inhibition as a Conserved Therapeutic Vulnerability in Osteosarcoma

Ankita Gupte, Emma K Baker, Soo-San Wan, Elizabeth Stewart, Amos Loh, Anang A Shelat, Cathryn M Gould, Alistair M Chalk, Scott Taylor, Kurt Lackovic, Asa Karlstroem, Anthony J Mutsaers, Jayesh Desai, Piyush B Madhamshettiwar, Andrew CW Zannettino, Chris Burns, David CS Huang, Michael A Dyer, Kaylene J Simpson, Carl R Walkley



PURPOSE: Osteosarcoma is the most common cancer of bone occurring mostly in teenagers. Despite rapid advances in our knowledge of the genetics and cell biology of osteosarcoma, significant improvements in patient survival have not been observed. The identification of effective therapeutics has been largely empirically based. The identification of new therapies and therapeutic targets are urgently needed to enable improved outcomes for osteosarcoma patients. EXPERIMENTAL DESIGN: We have used genetically engineered murine models of human osteosarcoma in a systematic, genome-wide screen to identify new candidate therapeutic targets. We performed a genome-wide siRNA screen, with or without doxor..

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Awarded by AACR-Aflac Inc, Career Development Award for Pediatric Cancer Research

Awarded by Cancer Council of Victoria

Awarded by NHMRC

Awarded by LLS Specialized Center of Research

Funding Acknowledgements

This work was supported by grants from the AACR-Aflac Inc, Career Development Award for Pediatric Cancer Research (to C.R. Walkley; 12-20-10-WALK); Colin North (to C.R. Walkley); Zig Inge Foundation (to C.R. Walkley); 5-point foundation (to E.K. Baker); Cancer Council of Victoria (to C.R. Walkley and E.K. Baker; grant-in-aid APP1047593); NHMRC Career Development Award (to C.R. Walkley; APP559016); NHMRC Research Fellowship (to D.C.S. Huang; APP1043149); Cure Cancer Australia Foundation Fellowship (to E.K. Baker); NHMRC program grant (to D.C.S. Huang; APP1016701); LLS Specialized Center of Research (C. Burns and D.C.S. Huang; 7001-13); NHMRC IRIIS grant (to St. Vincent's Institute [SVI] and Walter and Eliza Hall Institute [WEHI]); in part by the Victorian State Government Operational Infrastructure Support Program (to SVI and WEHI); The Victorian Centre for Functional Genomics is funded by the Australian Cancer Research Foundation (ACRF), the Victorian Department of Industry, Innovation and Regional Development (DIIRD), the Australian Phenomics Network (APN), and supported by funding from the Australian Government's Education Investment Fund through the Super Science Initiative, the Australasian Genomics Technologies Association (AMATA), the Brockhoff Foundation and the Peter MacCallum Cancer Centre Foundation; M.A. Dyer is an Investigator of the Howard Hughes Medical Institute; C.R. Walkley is the Philip Desbrow Senior Research Fellow of the Leukaemia Foundation.