Mitochondrial DNA Mutations and Oxidative Phosphorylation Reprogramming in Colorectal Cancer and Breast Cancer: Systematic Review of Distinct Mitochondrial Mechanisms in Tumor Progressions
Keywords:
Mitochondrial Dysfunction, Oxidative Phosphorylation, Mitochondrial DNA, Reactive Oxygen Species, Breast Cancer, Colorectal Cancer, NeoplasmsAbstract
Background: Mitochondrial dysfunction with mitochondrial DNA (mtDNA) mutations and oxidative phosphorylation (OXPHOS) reprogramming have a significant role in cancer progression. The aim of the study was to mechanically compare different mechanisms of mitochondria in tumour development, both in breast and colorectal cancer. Methodology: It was a systematic review based on PRISMA guidelines 2020. The databases used in the search were PubMed, Scopus, Web of Science, and Google Scholar from 2020-2026. This was done by including clinical, experimental in vitro and in vivo studies that examined the role of mitochondrial DNA mutations and OXPHOS pathways in breast and colorectal cancer and excluding reviews, case reports, non-English studies, and irrelevant disease models. Newcastle-Ottawa Scale (NOS), Joanna Briggs Institute (JBI) checklist, ROBINS-I tool, modified in vitro tools, and SYRCLE tool were all used to assess risk of bias, with some certainty of evidence assessed using the GRADE framework. Results: 12 studies meet the inclusion criteria. Results have shown that OXPHOS reprogramming and the presence of the mutations in the mitochondrial DNA resulted in electron transport dysfunction, reactive oxygen species generation, and ATP production, all of which were contributing factors to tumour progression, metabolic adaptation, and therapeutic resistance. Mitochondrial pathways also had an effect on tumor microenvironment and prognosis. The risk of bias was moderate in general and the certainty of evidence was low according to GRADE assessment. Conclusion: Mitochondrial changes are the main focus of cancer development and are potential therapeutic targets. It is recommended that future research should be done on clinical validation and development of mitochondrial-targeted therapy to treat cancer on a personal basis.
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