Cancer stem cells are the cells within a tumour that can self-renew indefinitely and give rise to more differentiated cell types. We explore the concept that multiple cancer stem cell phenotypes exist within individual tumours, and investigate the underlying cellular plasticity that drives this stem cell heterogeneity. The presence of multiple cancer stem cell phenotypes, potentially generated by re-activation of latent developmental plasticity, may help explain the wide variation in progression and therapeutic response seen between tumours. In identifying the molecular events underlying cellular plasticity, our research has the potential to uncover novel avenues for therapeutic intervention in cancer. More generally, we aim to further our understanding of the mechanisms underlying the remarkable cellular plasticity that exists in both normal and neoplastic tissue, including in development and tissue regeneration.

Our human cancer cell line work is backed up by analysis of cancer stem cell sub-populations in human tumour specimens, including comparisons with data on clinical progression. In time, such analyses might enable the tailoring of clinical decisions to the particular distribution of cancer stem cell sub-populations within each individual tumour.

We focus mainly on oral squamous cell carcinoma, a tumour type that has an annual worldwide incidence of over 300000 cases and a mortality rate of 48%.

Key questions arising from our work to date, and on which we are focussing our current efforts, are the following; 1) What is the molecular basis underlying the diversity of cancer stem cell phenotypes in squamous cell carcinoma? 2) Is the generation of multiple cancer stem cell phenotypes dependent on processes that occur in development? 3) Do differences in the incidence of cancer stem cell phenotypes between tumours help drive variation in progression and response to therapy? 4) How can we improve the modelling of human tumours, in order to accurately predict cellular behaviour and response to therapy?

Further details of the different projects underway in our lab can be found in the profiles for each of the Lab members.