Journal article

Smac mimetics LCL161 and GDC-0152 inhibit osteosarcoma growth and metastasis in mice

TM Shekhar, IJG Burvenich, MA Harris, A Rigopoulos, D Zanker, A Spurling, BS Parker, CR Walkley, AM Scott, CJ Hawkins

BMC Cancer | BMC | Published : 2019

Open access

Abstract

Background: Current therapies fail to cure over a third of osteosarcoma patients and around three quarters of those with metastatic disease. "Smac mimetics" (also known as "IAP antagonists") are a new class of anti-cancer agents. Previous work revealed that cells from murine osteosarcomas were efficiently sensitized by physiologically achievable concentrations of some Smac mimetics (including GDC-0152 and LCL161) to killing by the inflammatory cytokine TNFα in vitro, but survived exposure to Smac mimetics as sole agents. Methods: Nude mice were subcutaneously or intramuscularly implanted with luciferase-expressing murine 1029H or human KRIB osteosarcoma cells. The impacts of treatment with G..

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Grants

Funding Acknowledgements

This study was funded by a grant from The Kids' Cancer Project, a Sarcoma Research Grant from the GPA Andrew Ursini Charitable Fund and the Australasian Sarcoma Study Group, and a Grant-in-Aid from the Cancer Council Victoria. These organizations financed the work but played no role in the design of the study and collection, analysis, and interpretation of data or in writing the manuscript.