The double-edged sword of SASP in breast cancer: from tumor suppression to progression and therapy resistance
TL;DR
This review focuses specifically on BC and integrates pathogenic mechanism analysis with inter-subtype comparisons across BC subtypes and existing SASP-targeted therapeutic strategies are discussed, with the aim of providing novel insights into the potential role of SASP in BC treatment.
Abstract
The senescence-associated secretory phenotype (SASP) represents a complex and dynamic collection of bioactive factors secreted by senescent cells, which exerts dual regulatory effects on breast cancer (BC) progression. When SASP is transiently expressed, it promotes tumor suppression by recruiting immune cells to enhance immunosurveillance against senescent cells, and by transmitting paracrine signals that inhibit cancer cell proliferation. In contrast, when senescent cells cannot be cleared in a timely manner and SASP transitions to a chronic, persistent state, it drives tumor progression through multiple mechanisms, including the promotion of chronic inflammation, induction of epithelial-to-mesenchymal transition (EMT), and facilitation of immune evasion. Unlike previous pan-cancer reviews that largely rely on descriptive literature summaries, this review focuses specifically on BC and integrates pathogenic mechanism analysis with inter-subtype comparisons across BC subtypes. The dual roles of SASP in BC are systematically examined along three dimensions: cellular origin, temporal dynamics, and SASP component heterogeneity. Furthermore, existing SASP-targeted therapeutic strategies are discussed, with the aim of providing novel insights into the potential role of SASP in BC treatment.