Unveiling the complexity of cellular senescence in cancers: From mechanism to therapeutic opportunities

Abstract Cellular senescence is characterized by a sustained and irreversible cessation of cell proliferation in response to diverse environmental stimuli. However, senescent cells exhibit strong metabolic activity and release a range of cytokines and inflammatory mediators into the tumor microenvironment, collectively referred to as the senescence‐associated secretory phenotype (SASP). In recent years, to develop new therapies for cancers, researchers have conducted extensive studies on the mechanism of cancer cell senescence and revealed that induction of cancer cell senescence could effectively suppress cancer progression. However, it has been documented that cellular senescence not only inhibits cancer initiation but also contributes significantly to cancer progression in some cases. Hence, it is imperative to comprehend the correlation between cellular senescence and tumorigenesis, and discuss the potential utilization of cellular senescence mechanisms to suppress cancer progression, which lays a theoretical foundation for new drugs to treat cancers. In this review, we first provide an overview of the discovery of cellular senescence and its key milestone events. Meanwhile, this review examines the major stimulus for the induction of senescence, and provides an overview of the categorization of cellular senescence. Subsequently, an examination of the primary regulatory mechanisms of cellular senescence is discussed, followed by a summary of the control of the SASP expression and its dual biological roles in cancers. Additionally, we also provide an overview of common biomarkers utilized in the identification of cellular senescence. Finally, this review investigates the efficacy of the “One‐Two punch” sequential treatment approach for cancers, and examines the emerging challenges of this novel approach.