The therapy-induced senescence-associated secretory phenotype and epithelial-mesenchymal transition axis in ovarian cancer: molecular mechanisms and therapeutic opportunities.

INTRODUCTION

Therapy-induced senescence (TIS) is an important response to anticancer treatments in ovarian cancer, which can trigger the senescence-associated secretory phenotype (SASP) that may contribute to epithelial-mesenchymal transition (EMT), tumor migration, invasion, and adhesion. This review delineates the molecular mechanisms through linking TIS-mediated SASP to EMT and evaluates emerging therapeutic opportunities.

AREAS COVERED: We discuss key regulatory pathways including cGAS-STING, NF-κB, p53, and STAT3 that orchestrate SASP components such as IL-6, IL-8, and TGF-β to activate EMT transcription factors. Bioinformatics analyses of clinical datasets identify SASP factors (IL-6, AREG, c-JUN, TIMP1, THBS1) as critical EMT mediators, with hub genes including COL4A2, COL5A2, PDGFRB, and FBN1 involved in ECM remodeling and cell adhesion. SASP promotes ovarian cancer cell adhesion through MMP-mediated ECM degradation, release of matrix-bound growth factors, generation of adhesive fragments, and induction of mesothelial-mesenchymal transition. We evaluate emerging therapeutic strategies targeting this axis, including senolytics to eliminate senescent cells, senomorphics to suppress SASP secretion, and targeted inhibition of specific SASP components.

EXPERT OPINION: Although preclinical advances are promising, challenges in model systems and real-time SASP monitoring remain; future integrated multi-omics analyses and personalized therapeutic approaches are needed to translate these findings into improved ovarian cancer outcomes.