Murillo Carrasco Alexis Germán, Chammas Roger, Furuya Tatiane Katsue
Centro de Investigação Translacional em Oncologia (LIM24), Instituto do Câncer do Estado de São Paulo (ICESP), Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil; Comprehensive Center for Precision Oncology, Universidade de São Paulo, São Paulo, Brazil.
Clinics (Sao Paulo). 2025 Jan 29;80:100570. doi: 10.1016/j.clinsp.2024.100570. eCollection 2025.
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.
线粒体是对细胞重要功能至关重要的动态细胞器，包括三磷酸腺苷（ATP）生成、细胞凋亡调控和钙稳态。越来越多的研究强调了线粒体DNA（mtDNA）含量以及其改变在包括癌症在内的各种疾病发生和发展中的重要性。mtDNA的高突变率和易受损性使这些改变成为用于癌症诊断、监测疾病进展、检测转移以及预测不同肿瘤类型治疗耐药性的有价值生物标志物。本综述探讨了mtDNA改变在精准肿瘤学中的新作用，强调了它们在治疗诊断学中的潜力。作者们探究了mtDNA突变促进肿瘤发生和治疗耐药性的机制、异质性在癌症生物学中的影响，以及基于mtDNA的诊断与当前治疗策略的整合。此外，作者们强调了目前用于研究癌症中mtDNA改变的实验工具和模型，包括先进的测序技术和动物模型。
