Mitochondria in Cancer Stem Cells: From an Innocent Bystander to a Central Player in Therapy Resistance

Stem Cells Cloning. 2023 Aug 23:16:19-41. doi: 10.2147/SCCAA.S417842. eCollection 2023.


Cancer continues to rank among the world's leading causes of mortality despite advancements in treatment. Cancer stem cells, which can self-renew, are present in low abundance and contribute significantly to tumor recurrence, tumorigenicity, and drug resistance to various therapies. The drug resistance observed in cancer stem cells is attributed to several factors, such as cellular quiescence, dormancy, elevated aldehyde dehydrogenase activity, apoptosis evasion mechanisms, high expression of drug efflux pumps, protective vascular niche, enhanced DNA damage response, scavenging of reactive oxygen species, hypoxic stability, and stemness-related signaling pathways. Multiple studies have shown that mitochondria play a pivotal role in conferring drug resistance to cancer stem cells, through mitochondrial biogenesis, metabolism, and dynamics. A better understanding of how mitochondria contribute to tumorigenesis, heterogeneity, and drug resistance could lead to the development of innovative cancer treatments.

Keywords: cancer stem cells; drug resistance; metabolic dysfunction; mitochondria; therapy.

Publication types

  • Review

Grants and funding

The authors would like to acknowledge that no external funding was received for the preparation of this review article.