We are currently undertaking an analysis of the transcriptome and genome of melanoma stem cells. These studies are identifying molecules that are differentially expressed on putative stem cells but not their progeny. The transcriptome analysis is enabling a rational identification of pathways which are differentially activated in stem-like cells. Critical molecules within these would appear to be prime targets for anti-cancer therapy, so long as they are not also critical for the self-renewal of somatic stem or germ cells. It should be possible to determine whether currently available anti-cancer drugs such as receptor tyrosine kinase inhibitors act on these cells. Such drugs have established safety records and can be tested in the cancer colony forming assays. This assay is potentially suitable for adaptation to a high-throughput screening assay and the feasibility of this will be explored during the course of this project. Promising pharmacological agents will subsequently be assessed in a murine model.