Dysregulation of mitophagy and mitochondrial homeostasis in cancer stem cells: Novel mechanism for anti-cancer stem cell-targeted cancer therapy

Abstract

Despite the potential of cancer medicine, cancer stem cells (CSCs) associated with chemoresistance and disease recurrence are the significant challenges currently opposing the efficacy of available cancer treatment options. Mitochondrial dynamics involving the fission–fusion cycle and mitophagy are the major contributing factors to better adaptation, enabling CSCs to survive and grow better under tumour micro-environment-associated stress. Moreover, mitophagy is balanced with mitochondrial biogenesis to maintain mitochondrial homeostasis in CSCs, which are necessary for the growth and maintenance of CSCs and regulate metabolic switching from glycolysis to oxidative phosphorylation. In this review, we discuss different aspects of mitochondrial dynamics, mitophagy, and mitochondrial homeostasis and their effects on modulating CSCs behaviour during cancer development. Moreover, the efficacy of pharmacological targeting of these cellular processes using anti-CSC drugs in combination with currently available chemotherapeutic drugs improves the patient's survival of aggressive cancer types.