Fate Bifurcation of Cellular Senescence: Dynamic Regulation from Tumor Suppression to Recurrence Risk

Cellular senescence is a state of stable cell cycle arrest triggered by various internal and external stressors. It represents an important tumor-suppressive mechanism that effectively prevents the proliferation of damaged cells. During tumor initiation and progression, cellular senescence plays a dual and paradoxical role. On one hand, it induces cell cycle arrest to inhibit the development of tumors in potentially malignant cells. On the other hand, it can promote tumor progression through the senescence-associated secretory phenotype (SASP), which enhances inflammation and extracellular matrix remodeling. This review outlines the definition and key characteristics of cellular senescence and analyzes different senescence-inducing stimuli along with their underlying molecular mechanisms. It further discusses the molecular basis for the maintenance of stable senescence, mechanisms to escape growth arrest, and how these cells contribute to tumor recurrence through dedifferentiation and acquisition of stemness properties. Additionally, the dual regulatory role of SASP in tumor progression is examined. In terms of cancer therapy, with a deeper understanding of the mechanisms of senescent cells, treatment strategies are gradually shifting from single senescence-inducing approaches to more comprehensive combinatorial strategies. Meanwhile, the integration of single-cell omics technologies with artificial intelligence and machine learning offers new prospects for personalized therapy.