Preclinical Modelling of Paediatric Cancer Evolution

How cancer cells adapt over time

Cancer evolution is often described as a purely genetic process, driven by the gradual accumulation of mutations.

However, increasing evidence shows that non-genetic cell-state changes play a central role in how cancer cells survive therapy and eventually relapse.

Our research focuses on understanding how phenotypic plasticity — the ability of cells to reversibly change state — interacts with genetic evolution and selection to shape tumour behaviour over time.

A plasticity-first view of cancer evolution

Rather than viewing plasticity as a by-product of genetic change, we explore the idea that:

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Cell-state switching can actively shape evolutionary trajectories by determining which cells survive, expand, and acquire mutations under treatment.

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In this framework, plasticity:

• alters the effective population structure of tumours
• changes the timing and strength of selection
• creates windows of vulnerability or resilience during therapy

Understanding these dynamics is essential for predicting long-term outcomes.

Quantifying plasticity at single-cell resolution

To study plasticity directly, we develop and apply approaches that allow us to: