Senescence-associated mitochondrial dysfunction as a therapeutic target in ovarian cancer: Challenges and opportunities

Senescence-associated mitochondrial dysfunction (SAMD) links aging, metabolic reprogramming, and therapy resistance in ovarian cancer. Persistent damage to mitochondrial DNA (mtDNA), impaired mitochondrial quality control, and disrupted mitochondrial fusion and fission dynamics compromise electron transport (ET) and membrane potential, yielding chronic mitochondrial reactive oxygen species. This, in turn, drives a senescence-associated secretory phenotype, which includes proinflammatory cytokines, matrix proteases, and pro-angiogenic factors. This secretory phenotype alters the tumor microenvironment in ways that make the cells more resistant to cell death. In this review, we provide comprehensive insights from preclinical and translational clinical studies to map mechanistic connections and outline pragmatic measurement strategies. Our goal is to explore whether SAMD can move from being merely a descriptive hallmark to a measurable biomarker and a practical therapeutic target for restoring chemosensitivity.