Developmental plasticity as a framework for paediatric cancer metastasis

Green, D ORCID: 0000-0002-0217-3322 and Sexton, DW ORCID: 0000-0003-3344-3150 (2026) Developmental plasticity as a framework for paediatric cancer metastasis. Trends Open. ISSN 3117-3470

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Abstract

Metastasis is the principal cause of cancer-related mortality in children, yet its biological origins remain incompletely understood.Paediatriccancersfrequently combine low mutation burdens with structural genomic alterations and phenotypic heterogeneity, suggesting that metastatic progression reflects interactions between genetic evolution and cellular plasticity. Here, we integrate genomic, epigenomic, developmental, and single-cell evidence to examine how oncogenic lesions and developmental origin define accessible cellular states, while epigenetic, metabolic, and microenvironmental signals regulate transitions between them. We propose a developmental plasticity framework in which genetic architecture constrains the cellular state landscape, while phenotypic adaptation shapes metastatic behaviour. We discuss evidence distinguishing plasticity from clonal selection, mechanisms driving state transitions, and opportunities to therapeutically intercept metastasis-permissive states or exploit vulnerabilities created during adaptation.

Item Type:	Article
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) R Medicine > RS Pharmacy and materia medica
Divisions:	Pharmacy and Biomolecular Sciences
Publisher:	Elsevier
Date of acceptance:	2 October 2026
Date of first compliant Open Access:	10 November 2026
Date Deposited:	10 Nov 2026 11:28
Last Modified:	10 Nov 2026 11:28
DOI or ID number:	10.1016/j.treopn.2026.10.002
URI:	https://researchonline.ljmu.ac.uk/id/eprint/29854

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