Cancer Research UK Edinburgh Centre

Defining the cellular transition states mediating colorectal cancer cell plasticity

Supervisor: Dr Kevin Myant

Kevin Myant research image

Colorectal cancer is the second commonest cause of cancer related mortality in the UK with the majority of deaths due to spread of the disease to other organs. Metastatic colorectal cancers are enriched in cancer stem cells, a small population of cells within a tumour that drive tumour growth, progression and resistance to therapy. Therapeutic targeting of cancer stem cells is an attractive prospect that has been proposed as a way of suppressing tumour growth and metastasis in a specific, highly targeted manner. However, recent reports have demonstrated that upon depletion of cancer stem cells, differentiated tumour cells are able to dedifferentiate, acquire stem cell properties and subsequently drive tumour growth (Figure 1). This ‘cancer cell plasticity’ is a significant barrier for the development of therapies targeting cancer stem cells and also plays a key role in mediating resistance to conventional anti-cancer therapeutics. Despite the clear clinical implications, the cellular changes that drive the transition from differentiated tumour cell to cancer stem cell are poorly understood.

The aim of this project is to determine the mechanisms driving the cellular transition states mediating colorectal cancer cell plasticity following cancer stem cell depletion and therapy treatment. The student will utilise single cell RNAseq, 3D organoid culture, CRISPR/Cas9 genome editing and mouse metastasis models to map changes in cellular plasticity and determine the mechanisms driving them. Both cell intrinsic and cell extrinsic factors will be investigated, with a particular focus on how the tumour microenvironment mediates this process and how it might be exploited therapeutically.

Kevin Myant Research Group