Exploring phenotypic plasticity as a mechanism of early adaptation to treatment in neuroblastoma
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Embargo End Date
2027-01-08
ICR Authors
Authors
Hamer, S
Document Type
Thesis or Dissertation
Date
2026-01-08
Date Accepted
Abstract
Neuroblastoma is a paediatric tumour characterised by extensive clinical heterogeneity, ehich spans from spontaneous regression to therapeutic resistance or relapse. Much of this diverse clinical presentation, is thought to be driven by phenotypic plasticity and heterogeneity in tumour cell populations. Phenotypic plasticity is a key mechanism through which tumour cells may adapt and survive changing environments by changing their phenotype without altering their genotype. Recent studies have emphasized the need to understand the molecular factors controlling phenotypic
plasticity, as a means to generate more effective therapies that improve treatment outcomes in neuroblastoma patients. To this end, within this thesis I explored the role of phenotypic plasticity as a mechanism to early adaptation to treatment in neuroblastoma. Using molecular and functional characterisation assays and drug response assays, I demonstrate the clinical and molecular
implications of phenotypic composition in neuroblastoma. Utilising cellular barcoding technologies and single cell resolution transcriptomics, I demonstrated that phenotypic plasticity is be enriched following neuroblastoma treatment responses. Experimental evolution and reaction norms methods
demonstrated phenotypic plasticity was a heterogeneous trait in neuroblastoma populations. Using single nuclei multiomics technologies, I characterised the molecular features defining plastic
neuroblastoma cells and identified potential TFs and pathways regulating phenotypic plasticity. Finally, I defined regulatory developmental pathways which regulate phenotypic plasticity during treatment response in neuroblastoma.
Citation
2026
DOI
Source Title
Publisher
Institute of Cancer Research (University Of London)
ISSN
eISSN
Collections
Research Team
Preclin Paed Cancer Evo