TY  - EJOU
AU  - Zhu, Yan 
AU  - Zhang, Wenhao 
AU  - Gao, Yunqiu 

TI  - Senescence-associated secretory phenotype in urological cancers: molecular mechanisms, tumor microenvironment modulation, and therapeutic targeting
T2  - European Cytokine Network

PY  - 2026
VL  - 37
IS  - 3
SN  - 1952-4005

AB  - Cellular senescence is a durable stress response with double effects on cancer. Although stable cell-cycle arrest may initially restrict tumor growth, senescent tumor and stromal cells remain metabolically active and can remodel the tumor microenvironment through the senescence-associated secretory phenotype (SASP). This review synthesizes current evidence on therapy-induced and tumor-intrinsic senescence in prostate, bladder, and kidney cancers, focusing on molecular regulation and context-dependent SASP effects. We discuss how NF-κB, JAK/STAT3, cGAS-STING, and p38 MAPK regulate SASP composition. These pathways help determine the composition of the SASP, including the cytokines, chemokines, growth factors, and matrix-remodeling enzymes released by senescent cells. These SASP factors can recruit immunosuppressive myeloid cells, impair T-cell function, alter extracellular matrix organization, and support invasion, metastasis, and treatment response. The available evidence indicates that outcome depends on the inducing stimulus, cellular source, immune context, and duration of the response. Senolytics, senomorphics, and combinations with immunotherapy are promising, but evidence in urological cancers remains largely preclinical. Clinical translation will require validated multi-marker assays, longitudinal sampling, and prospective trials that distinguish transient immunogenic senescence from persistent immunosuppressive senescence.
KW  - Cellular senescence; senescence-associated secretory phenotype; urological cancer; tumor microenvironment; senolytics; senomorphics

DO  - 10.32604/ecn.2026.087229