Targeting cIAP2 in a novel senolytic strategy prevents glioblastoma recurrence after radiotherapy

ABSTRACT: Glioblastomas (GBM) are treated with high doses of ionizing radiation (IR), yet these tumors recur quickly, and the recurrent tumors are highly therapy resistant. Here, we report that IR-induced senescence of tumor cells counterintuitively spurs GBM recurrence, driven by the senescence-associated secretory phenotype (SASP). We find that irradiated GBM cell lines and patient derived xenograft (PDX) cultures undergo senescence, upregulate SASP genes, and secrete SASP factors that collectively activate the JAK-STAT3 and NF-kB pathways in non-senescent GBM cells, thereby promoting tumor cell proliferation and SASP spreading. We find that the cellular inhibitor of apoptosis protein 2 (cIAP2) is a critical survival factor for senescent glioma cells. Importantly, SMAC mimetics targeting cIAP2 act

SUBMITTER: Nozomi Tomimatsu 

PROVIDER: S-SCDT-10_1038-S44321-025-00201-X | biostudies-other |

REPOSITORIES: biostudies-other