Cancer Cell Plasticity

Our group investigates the intrinsic and extrinsic mechanisms by which cellular plasticity mediates cancer initiation and progression, to identify prognostic markers and potential therapeutic targets.

Dr Miguel Bernabé-Rubio

Junior Group Leader / CRUK Career Development Fellow

UCL Cancer Institute

Research focus

Cancer cells undergo molecular and phenotypic changes known as cellular plasticity, which enable cells to alter their identity. This plasticity enables the acquisition of stem cell-like properties, drives invasiveness, and contributes to therapy resistance. Despite its clinical significance, the underlying molecular mechanisms remain poorly understood.

Plasticity is also a feature of normal tissues. In response to injury, specialised cells can revert to a stem cell-like state through a process known as dedifferentiation. Whereas wound healing involves transient plasticity, cancer is characterised by sustained plasticity, suggesting a mechanistic link between chronic injury and tumour development. Understanding these mechanisms could reveal new strategies to target or exploit plasticity for therapy.

Our group aims to understand the cellular and molecular mechanisms by which regenerative programmes promote cancer initiation and progression, with a particular focus on dedifferentiation. We are investigating how cancer cells transition between different cellular states and how microenvironmental factors, including mechanical stress, regulate this plasticity. Using cutaneous squamous cell carcinoma – the second most prevalent epithelial malignancy – as a model system, we integrate lineage tracing, single-cell-RNA-seq, advanced microscopy, and cell biology approaches to identify cancer-specific vulnerabilities that can be leveraged for therapeutic intervention.