The ATR inhibitor tuvusertib (M1774) sensitizes prostate carcinoma to natural killer cell-mediated cytotoxicity, which is further augmented by the IL-15 receptor superagonist N-803.

ABSTRACT: High levels of replication stress make cancer cells vulnerable to therapies targeting DNA damage response (DDR) proteins, such as ataxia telangiectasia and Rad3-related (ATR) protein kinase. ATR is a key mediator of the replication stress response and plays a vital role in maintaining genomic stability. This study investigates the immunomodulatory potential of the ATR inhibitor (ATRi) tuvusertib to improve the targeting of prostate cancer (PCa) by immunotherapy. Tuvusertib pretreatment sensitized human PCa cells (DU145 and 22Rv1) to PBMC-derived natural killer (NK)-mediated lysis. Flow cytometric analysis identified upregulation of death receptor tumor-necrosis factor-related apoptosis-inducing ligand receptor 2 (TRAIL-R2), NKG2D ligand ULBP-1, and programmed death-ligand 1 (PD-L1) as a po

SUBMITTER: Lee CA 

PROVIDER: S-EPMC12717344 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature