The cancer stem cell hypothesis is a model that explains many observed features of cancer and may explain why previous treatments are less effective than hoped. The hypothesis proposes that only a subset of cells within each cancer has the capacity to maintain cancer growth and metastasise to form new tumours. Effective therapy requires these cells to be effectively eradicated. There is evidence that these cells have biologically distinct characteristics and thus may express targets that differ from their progeny, which populate the bulk of the tumour. Consequently the failure of cancer therapy may occur because the wrong cancer-related molecules are targeted. If molecules with functional effects on the stem-like nature of these cells can be identified, it may be possible to target them specifically.

We have established models in melanoma that have allowed us to isolate cells with stem-like properties and to evaluate them phenotypically, genotypically and functionally. We are now applying these methods to prostate and bladder cancers. In particular, we will investigate the effects of altering expression of particular molecules ("cancer-testis antigens") on the properties of these cells in vitro and in vivo in terms of their stem-like behaviour and their susceptibility to immune attack.