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Osteosarcoma in the Post Genome Era: Preclinical Models and Approaches to Identify Tractable Therapeutic Targets

  • Cancer-induced Musculoskeletal Diseases (E Keller and J Sterling, Section editors)
  • Published:
Current Osteoporosis Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Osteosarcoma (OS) is the most common cancer of bone, yet is classified as a rare cancer. Treatment and outcomes for OS have not substantively changed in several decades. While the decoding of the OS genome greatly advanced the understanding of the mutational landscape of OS, immediately actionable therapeutic targets were not apparent. Here we describe recent preclinical models that can be leveraged to identify, test, and prioritize therapeutic candidates.

Recent Findings

The generation of multiple high fidelity murine models of OS, the spontaneous disease that arises in pet dogs, and the establishment of a diverse collection of patient-derived OS xenografts provide a robust preclinical platform for OS. These models enable evidence to be accumulated across multiple stages of preclinical evaluation. Chemical and genetic screening has identified therapeutic targets, often demonstrating cross species activity. Clinical trials in both PDX models and in canine OS have effectively tested new therapies for prioritization.

Summary

Improving clinical outcomes in OS has proven elusive. The integrated target discovery and testing possible through a cross species platform provides validation of a putative target and may enable the rigorous evaluation of new therapies in models where endpoints can be rapidly assessed.

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Funding

Work in CRW’s laboratory is supported by National Health and Medical Research Council Australia project grant (NHMRC; APP1102004); a Melbourne Research Scholarship (W.C-T. University of Melbourne); Victorian Cancer Agency Research Fellowship (C.R.W. MCRF15015); the Office of the Assistant Secretary of Defense for Health Affairs through the Peer Reviewed Cancer Research under Award No. W81XWH-15-1-0315 (to C.R.W.). Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Department of Defense (USA); Work in CRW’s laboratory was enabled in part by the Victorian State Government Operational Infrastructure Support (to St Vincent’s Institute). Work in AJM’s laboratory is supported by the OVC Pet Trust Foundation and is enabled by infrastructure support from the Canada Foundation for Innovation.

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Authors and Affiliations

  1. St. Vincent’s Institute, 9 Princes St, Fitzroy, VIC, 3065, Australia

    Wilson Castillo-Tandazo & Carl R. Walkley

  2. Department of Medicine, St. Vincent’s Hospital, University of Melbourne, Fitzroy, VIC, 3065, Australia

    Wilson Castillo-Tandazo & Carl R. Walkley

  3. Department of Biomedical Sciences, Ontario Veterinary College, Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, Canada

    Anthony J. Mutsaers

  4. Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne, VIC, 3000, Australia

    Carl R. Walkley

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  1. Wilson Castillo-Tandazo
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Correspondence to Anthony J. Mutsaers or Carl R. Walkley.

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Conflict of Interest

Carl Walkley reports grants from National Health and Medical Research Council, Australia, Victorian Cancer Agency Research Fellowship, and Victorian State Government Operational Infrastructure Support, during the conduct of the study.

Wilson Castillo-Tandazo reports grants from Melbourne Research Scholarship, University of Melbourne, during the conduct of the study.

Anthony Mutsaers reports grants from OVC Pet Trust Foundation and the Canada Foundation for Innovation, during the conduct of the study.

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Castillo-Tandazo, W., Mutsaers, A.J. & Walkley, C.R. Osteosarcoma in the Post Genome Era: Preclinical Models and Approaches to Identify Tractable Therapeutic Targets. Curr Osteoporos Rep 17, 343–352 (2019). https://doi.org/10.1007/s11914-019-00534-w

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