Targeting Cellular Senescence for Cancer Therapy

Abstract

Cellular senescence is a permanent state of growth arrest that develops when cells encounter various forms of physiological or pathological stress. Although senescence initially functions as a protective mechanism by preventing the proliferation of damaged cells, persistent senescent cells can alter the surrounding tissue environment through the release of bioactive molecules collectively known as the senescence-associated secretory phenotype (SASP). These secretions may promote chronic inflammation, tumor progression, metastasis, and resistance to anticancer therapy. Consequently, cellular senescence has emerged as both a biological barrier to cancer and a promising therapeutic target. Recent advances have led to the development of strategies that either induce senescence in malignant cells or selectively eliminate harmful senescent cells using senolytic agents while suppressing detrimental SASP signaling through senomorphic therapies. In addition, combining senescence-targeted interventions with chemotherapy, radiotherapy, immunotherapy, and molecularly targeted therapies offers new opportunities to improve treatment efficacy and reduce disease recurrence. This review summarizes the biological mechanisms regulating cellular senescence, highlights its contrasting roles in cancer development, discusses emerging therapeutic approaches, and outlines current challenges and future directions for translating senescence-based therapies into clinical oncology.