The Bidirectional Role of Cellular Senescence in the Treatment of Ovarian Cancer

Cellular senescence plays a complex and crucial dual role in ovarian cancer treatment: it serves as both an important tumor suppression mechanism and a potential driver of drug resistance and recurrence. This review systematically examines the intricate regulatory network of cellular senescence, encompassing multiple pathways including telomere dysfunction, DNA damage response, epigenetic remodeling, hormone signaling, and metabolic reprogramming. Studies have demonstrated that core therapeutic modalities, such as platinum-based chemotherapy, PARP inhibitors, and CDK4/6 inhibitors, can exert anti-tumor effects by inducing cellular senescence; however, their efficacy is significantly influenced by the senescence-associated secretory phenotype (SASP). Specific SASP components can activate immune surveillance, whereas others promote tumor progression, acquisition of stem cell-like characteristics, and therapeutic resistance. It is this "anti-tumor versus pro-tumor" paradox that renders senescent cells a critical variable determining treatment outcomes. In light of this, emerging strategies aim to precisely modulate the senescence process, including the use of epigenetic drugs to induce senescence, targeting metabolic vulnerabilities to eliminate senescent cells, and intervening in deleterious SASP to improve the tumor microenvironment. Integrating such strategies with conventional therapies holds promise for overcoming the resistance bottleneck in ovarian cancer and opening new avenues for improving patient prognosis.