Cancer stem cells: mitochondria signalling pathway and strategies for therapeutic interventions

Cancer stem cells (CSCs) play a critical role in tumor initiation, progression, and resistance to therapy, making them a major hurdle in effective cancer treatment. Unlike bulk cancer cells, CSCs exhibit remarkable adaptability, allowing them to survive under metabolic stress and evade conventional therapies. Mitochondria, as central regulators of cellular metabolism and apoptosis, are integral to CSC function. They facilitate metabolic reprogramming, redox balance, and stress adaptation, thereby enhancing CSC survival, self-renewal, and resistance to treatment. Dysregulated mitochondrial dynamics, including alterations in biogenesis, degradation, and signaling pathways, contribute to CSC maintenance and therapeutic resistance. Furthermore, mitochondrial membrane integrity and oxidative stress regulation determine CSC fate, influencing their ability to withstand chemotherapy and radiotherapy. Recent advances have identified mitochondrial-targeted strategies as promising approaches to impair CSC function and sensitize them to treatment. These include disrupting mitochondrial metabolism, inducing oxidative stress, and modulating mitochondrial quality control mechanisms. By understanding the intricate relationship between mitochondria and CSCs, new therapeutic strategies can be developed to selectively target CSCs, ultimately improving cancer treatment outcomes and preventing disease recurrence. This review provides an in-depth analysis of mitochondrial mechanisms in CSCs and their potential as therapeutic targets.