Integrating tumor-initiating cells into the paradigm for melanoma targeted therapy

There is growing evidence to suggest that not all cancer cells have similar levels of malignant potential and that tumor progression may be driven by specialized sub-sets of tumor initiating cells. It is likely that as tumor initiating cells have lower proliferation rates and enhanced survival mechanisms they may also drive drug resistance. Melanoma is known to be an exceptionally therapy resistant tumor, with no treatment yet identified to alter, the natural progression of the disseminated disease. In the current review, we discuss evidence for the existence of melanoma initiating cells and described possible therapeutic strategies to eradicate this population via the targeting of specific cell-surface markers or through the disruption of the interaction of the melanoma initiating cells with their local microenvironment. It is hoped that the targeting of melanoma initiating cells may be one approach to overcome the incredible therapy resistance of this tumor. (c) 2008 Wiley-Liss, Inc.