Objective

The aim of our research is to develop human cell culture models that have demonstrable relevance to human cancer and can replace mouse cancer models to enable more efficient drug discovery. Using an oral cancer cell line model, we have demonstrated that cancer stem cells (CSCs) drive tumour metastasis by undergoing epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET) to switch between epithelial and mesenchymal sub-populations (Biddle et al., 2011). We have further demonstrated heightened therapeutic resistance and metastatic potential of a novel CSC sub-population in oral cancer that exhibits a hybrid epithelial-mesenchymal phenotype and has a CD44^highEpCAM^lowCD24⁺ cell surface marker profile (Biddle et al., 2016). Hybrid CSCs with similar attributes have also been observed in breast cancer. This is therefore an important cell type that presents an attractive target for new therapies aimed at overcoming tumour therapeutic resistance and metastatic proclivity. We have now developed a method to enrich these CSCs in cell culture for therapeutic development (Biddle et al., 2016) and, using this method, we are able to test candidate therapeutic compounds and further dissect the molecular mechanisms driving the behaviour of these hybrid CSCs. We now aim to build collaborations for the identification of new therapeutic approaches that can target hybrid CSCs to overcome tumour therapeutic resistance and metastatic dissemination whilst limiting patient toxicity.