Melanoma stem cells: the past, present and future

Normal adult stem cells are characterized by their ability to selfrenew, as well as their ability to differentiate into various mature cell types. Cancer stem cells were first recognized by Bonnet et al, who showed a sub-portion of acute myelogenous leukemia (AML) stem cells could be identified and separated from AML cells in patients. This subset of AML cells were the only cells capable of transferring AML from the human patients to studied mice.1 The hypothesis of the existence of cancer stem cells gained more attention around 2001 when Reya et al pushed the notion that cancer stems cells are composed of a subset fraction of tumor cells that have the ability to maintain the tumor through self-renewal, conferring drug resistance, and inducing tumor relapse.2 These cancer stem cells have similar physiologic properties to normal adult stem cells, like self-renewal and differentiation. Normal stem cells had been shown to be resistant to cytotoxic agents compared to mature cell types, which is explained by anti-apoptotic mechanisms,3 quiescence,4 and high expression levels of ATP-binding cassette (ABC) transporters.5 Thus, the existence of cancer stem cells explains the reason why many treatments for metastatic tumors ultimately fail. Current treatments like chemotherapy and radiation can shrink, but not cure metastatic tumors. Frequently, these treatments do indeed target the bulk of tumor cells in the human body, but often, the drug therapy is unable to kill the cancer stem cells (due to inherited and/or acquired resistance), and thus the tumor can easily grow back. In recent years, cancer stem cells have been identified and isolated by characteristics of normal stem cells, like using tissue specific CD markers (The cluster of differentiation) and ABC transporter proteins.6 Research about targeted therapy in regard to these cancer stem cells has come in full swing over the past decade.