Clinical perspectives on mitochondria in cancer

Mitochondria have emerged as key determinants of cancer development and therapeutic response, extending their role beyond cellular energy production. Alterations in mitochondrial metabolism, mitochondrial DNA (mtDNA), dynamics, and quality control can support tumor growth and adaptation to the tumor microenvironment, while mitochondrial fitness also shapes the function and persistence of antitumor immune cells. Thus, mitochondrial biology represents a dynamic interface between tumor cells and the immune microenvironment. This review focuses on translating mitochondrial biology into clinical cancer applications in addition to recent advances in mitochondrial research. We evaluate mitochondrial alterations and mtDNA as diagnostic, prognostic, and predictive biomarkers, alongside strategies to selectively exploit cancer mitochondrial vulnerabilities while boosting antitumor immunity. We address key hurdles in therapeutic selectivity and discuss future perspectives for integrating mitochondrial targeting into precision oncology.