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febrer 28 @ 12:00 - 13:30

Investigating Adaptive phenotypic plasticity as an early cancer evolutionary driver in paediatric solid cancers for improved treatment strategies

Speaker: Alejandra Bruna, PhD. Team Leader in Preclinical Modelling of Paediatric Cancer Evolution – Centre for Paediatric Oncology Experimental Medicine| Centre for Cancer Evolution: Molecular Pathology Division – The Institute of Cancer Research. London, United Kingdom.


In paediatric cancers like neuroblastoma, limited genetic diversity emphasizes the role of phenotypic heterogeneity in driving malignancy. We investigated this phenomenon using experimental evolution and single-cell techniques in neuroblastoma preclinical models. Our findings reveal that neuroblastoma cells navigate multistable phenotypic landscapes, named plasticity systems. These finely regulate their topology and dynamics enabling tolerance, persistence, and regrowth in response to treatment. While preferential killing of adrenergic cells (ADRN), notably under cisplatin treatment, enriches drug-tolerant persister (DTP) populations with mesenchymal (MES) properties, we also observed phenotypic transitions contributing to DTP entry and exit. Additionally, single-cell-derived clone experiments unveiled a spectrum of heritable plasticity traits linked to functional properties, influencing DTP behaviour. Mathematical modelling supports the critical role of all cell phenotypes in evolutionary adaptation.

Collectively, our study depicts plasticity systems as key early cancer drivers of adaptive evolution in neuroblastoma through regulating the multistability and dynamics of phenotypic landscapes. These insights underscore the necessity of decoding plasticity for advancing long-term therapeutic effectiveness.


IRB Barcelona – Institut de Recerca Biomedica
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