Melanoma-initiating cells: a compass needed

Most tumours contain a heterogeneous population of cancer cells, which harbour a range of genetic mutations and have probably undergone deregulated differentiation programmes that allow them to adapt to tumour microenvironments. Another explanation for tumour heterogeneity might be that the cells within a tumour are derived from tumour-initiating cells through diverse differentiation programmes. Tumour-initiating cells are thought to constitute one or more distinct subpopulations within a tumour and to drive tumour initiation, development and meta-stasis, as well as to be responsible for their recurrence after therapy. Recent studies have raised crucial questions about the nature, frequency and importance of melanoma-initiating cells. Here, we discuss our current understanding of melanoma-initiating cells and outline several approaches that the scientific community might consider to resolve the controversies surrounding these cells.