Bull, E.C., Singh, A., Harden, A.M. et al. (29 more authors) (2025) Targeting metastasis in paediatric bone sarcomas. Molecular Cancer, 24. 153. ISSN 1476-4598
Abstract
Paediatric bone sarcomas (e.g. Ewing sarcoma, osteosarcoma) comprise significant biological and clinical heterogeneity. This extreme heterogeneity affects response to systemic therapy, facilitates inherent and acquired drug resistance and possibly underpins the origins of metastatic disease, a key component implicit in cancer related death. Across all cancers, metastatic models have offered competing accounts on when dissemination occurs, either early or late during tumorigenesis, whether metastases at different foci arise independently and directly from the primary tumour or give rise to each other, i.e. metastases-to-metastases dissemination, and whether cell exchange occurs between synchronously growing lesions. Although it is probable that all the above mechanisms can lead to metastatic disease, clinical observations indicate that distinct modes of metastasis might predominate in different cancers. Around 70% of patients with bone sarcoma experience metastasis during their disease course but the fundamental molecular and cell mechanisms underlying spread are equivocal. Newer therapies such as tyrosine kinase inhibitors have shown promise in reducing metastatic relapse in trials, nonetheless, not all patients respond and 5-year overall survival remains at ~ 50%. Better understanding of potential bone sarcoma biological subgroups, the role of the tumour immune microenvironment, factors that promote metastasis and clinical biomarkers of prognosis and drug response are required to make progress. In this review, we provide a comprehensive overview of the approaches to manage paediatric patients with metastatic Ewing sarcoma and osteosarcoma. We describe the molecular basis of the tumour immune microenvironment, cell plasticity, circulating tumour cells and the development of the pre-metastatic niche, all required for successful distant colonisation. Finally, we discuss ongoing and upcoming patient clinical trials, biomarkers and gene regulatory networks amenable to the development of anti-metastasis medicines.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2025. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
Keywords: | Ewing sarcoma; Osteosarcoma; Bone; Sarcoma; Metastasis |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Research Services (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 03 Jun 2025 14:43 |
Last Modified: | 03 Jun 2025 14:43 |
Status: | Published |
Publisher: | Springer Science and Business Media LLC |
Refereed: | Yes |
Identification Number: | 10.1186/s12943-025-02365-z |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:227334 |