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TNF-related apoptosis-inducing ligand (TRAIL) for bone sarcoma treatment: Pre-clinical and clinical data

Lookup NU author(s): Zakareya Gamie, Dr Emma Haagensen, Ricardo da Conceicao Ribeiro, Professor Kenneth Dalgarno, Dr Anja Krippner-Heidenreich, Craig Gerrand, Dr Kenneth RankinORCiD


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© 2017 Elsevier B.V. Bone sarcomas are rare, highly malignant mesenchymal tumours that affect teenagers and young adults, as well as older patients. Despite intensive, multimodal therapy, patients with bone sarcomas have poor 5-year survival, close to 50%, with lack of improvement over recent decades. TNF-related apoptosis-inducing ligand (TRAIL), a member of the tumour necrosis factor (TNF) ligand superfamily (TNFLSF), has been found to induce apoptosis in cancer cells while sparing nontransformed cells, and may therefore offer a promising new approach to treatment. We cover the existing preclinical and clinical evidence about the use of TRAIL and other death receptor agonists in bone sarcoma treatment. In vitro studies indicate that TRAIL and other death receptor agonists are generally potent against bone sarcoma cell lines. Ewing's sarcoma cell lines present the highest sensitivity, whereas osteosarcoma and chondrosarcoma cell lines are considered less sensitive. In vivo studies also demonstrate satisfactory results, especially in Ewing's sarcoma xenograft models. However, the few clinical trials in the literature show only low or moderate efficacy of TRAIL in treating bone sarcoma. Potential strategies to overcome the in vivo resistance reported include co-administration with other drugs and the potential to deliver TRAIL on the surface of primed mesenchymal or immune cells and the use of targeted single chain antibodies such as scFv-scTRAIL.

Publication metadata

Author(s): Gamie Z, Kapriniotis K, Papanikolaou D, Haagensen E, Da Conceicao Ribeiro R, Dalgarno K, Krippner-Heidenreich A, Gerrand C, Tsiridis E, Rankin KS

Publication type: Note

Publication status: Published

Journal: Cancer Letters

Year: 2017

Volume: 409

Pages: 66-80

Print publication date: 28/11/2017

Online publication date: 06/09/2017

Acceptance date: 28/08/2017

ISSN (print): 0304-3835

ISSN (electronic): 1872-7980

Publisher: Elsevier Ireland Ltd


DOI: 10.1016/j.canlet.2017.08.036