Stem cell transcription factor NANOG in cancers--is eternal youth a curse?

INTRODUCTION: Targeting cancer stem cells can be a more effective approach to treat cancer. NANOG is one of the key factors for maintaining the self-renewal ability and pluripotency of stem cells, including cancer stem cells. Overexpression of NANOG has been observed in various human malignancies. Several reports have suggested that NANOG contributes to carcinogenesis by initiating and preserving cancer stem cells. It is obvious that NANOG is also involved in establishing other hallmarks of cancer such as uncontrolled cell growth, chemoresistance, metastasis, and immune evasion. AREAS COVERED: This review will discuss the molecular properties and oncogenic roles of NANOG. The idea of using agents that inhibit the transcription factor to treat cancer is presented. Interfering with NANOG-mediated transcriptions using small interfering RNA, transcription factor decoy, genome editing, and small-molecule inhibitors may provide novel strategies to target cancer stem cells. EXPERT OPINION: As a pivotal controller in cancer stem cell maintenance and a positive regulator of various oncogenic pathways, NANOG may be an important target for cancer therapy. However, as a transcription factor, it is inherently difficult to target by pharmacological means. Novel approaches need to be explored before the inhibition of NANOG can be applied in a clinical setting.