Mitochondrial DNA alterations in precision oncology: Emerging roles in diagnostics and therapeutics

Mitochondria are dynamic organelles essential for vital cellular functions, including ATP production, apoptosis regulation, and calcium homeostasis. Increasing research has highlighted the significance of mitochondrial DNA (mtDNA) content and alterations in the development and progression of various diseases, including cancer. The high mutation rate and vulnerability of mtDNA to damage make these alterations valuable biomarkers for cancer diagnosis, monitoring disease progression, detecting metastasis, and predicting treatment resistance across different tumor types. This review explores the emerging roles of mtDNA alterations in precision oncology, emphasizing their potential in theranostics. The authors explore the mechanisms by which mtDNA mutations contribute to tumorigenesis and therapy resistance, the impact of heteroplasmy in cancer biology, and the integration of mtDNA-based diagnostics with current therapeutic strategies. Additionally, the authors highlight the experimental tools and models currently used to investigate mtDNA alterations in cancer, including advanced sequencing technologies and animal models.