Mitochondria play vital roles in various cellular processes, ranging from cellular metabolism to signal transduction and cell death regulation. As these properties are critical for cancer growth, the mitochondrion has recently become an attractive target for anti-cancer therapies. In addition, it has come to light that mitochondria are crucially involved in the regulation of stem cell identity, differentiation and fate. A similar role for mitochondria has been also demonstrated in malignant stem-like cells termed cancer stem cells (CSCs), which are implicated in progression and resistance of many tumors. In this review, we summarize different mitochondrial functions reported to promote acquisition and maintenance of CSC phenotype and discuss the rationale for their therapeutic targeting. Particular emphasis is given to therapeutics that act directly through modulation of these mitochondrial functions and have recently emerged as promising anti-CSC drugs in pre-clinical studies. This review highlights the intriguing aspects of mitochondrial biology that may have a crucial role in cancer initiation, progression, and resistance and which might facilitate pharmacological targeting. Indeed, understanding of mitochondrial function in the regulation of CSCs will promote the development of novel CSC-targeted therapeutic strategies, which could significantly improve the long-term survival of cancer patients.

Department of Experimental Biology Faculty of Science Masaryk University Brno Czech Republic

Department of Experimental Biology Faculty of Science Masaryk University Brno Czech Republic; International Clinical Research Center St Anne's University Hospital Brno Brno Czech Republic

Discipline of Pathology and Bosch Institute Faculty of Medicine and Health University of Sydney Sydney New South Wales 2006 Australia

Discipline of Pathology and Bosch Institute Faculty of Medicine and Health University of Sydney Sydney New South Wales 2006 Australia; Department of Experimental Biology Faculty of Science Masaryk University Brno Czech Republic; Department of Pathology and Biological Responses Nagoya University Graduate School of Medicine Nagoya 466 8550 Japan

Discipline of Pathology and Bosch Institute Faculty of Medicine and Health University of Sydney Sydney New South Wales 2006 Australia; Department of Experimental Biology Faculty of Science Masaryk University Brno Czech Republic; International Clinical Research Center St Anne's University Hospital Brno Brno Czech Republic

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