Cancer at its most fundamental level involves dysregulated and inexorable local and metastatic growth of abnormal cells, leading to patient mortality. The limited therapeutic benefit of current treatments is likely to relate to the existence of therapy-resistant, virulence-conferring cancer cell subpopulations. One of these subpopulations may coincide with Cancer Stem Cells (CSCs). CSCs are a distinct subpopulation of tumor cells that are capable of self-renewal and responsible for tumorigenic growth through differentiating to the bulk of non-tumorigenic progenies. Of importance, the failure of existing therapies to eradicate CSCs has been proposed to contribute to cancer metastasis and recurrence, emphasizing the need for novel therapies to target the virulence-conferring CSC populations. Herein, we observed that IFN-gamma may selectively inhibit minority populations of melanoma stem cells. It is intriguing to speculate that the anti-stem cell effects of IFN-gamma may synergize with conventional therapies that preferentially target more vulnerable non-stem cell populations, and further studies are now underway to address this important issue.

Clinical Implications:

IFN-gamma selectively targets the subpopulations of melanoma stem cells, which may account for resistance to therapy, metastasis, and recurrence. Anti-stem cell effects of IFN-gamma may synergize with conventional therapies that preferentially target more vulnerable non-stem cell populations.

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