Pharmacological NF-κB inhibition decreases cisplatin chemoresistance in muscle-invasive bladder cancer and reduces cisplatin-induced toxicities.

ABSTRACT: Most patients with muscle-invasive bladder cancer (MIBC) are not cured with platinum chemotherapy. Up-regulation of nuclear factor kappa light-chain enhancer of activated B cells (NF-κB) is a major mechanism underlying chemoresistance, suggesting that its pharmacological inhibition may increase platinum efficacy. NF-κB signaling was investigated in two patient cohorts. The Cancer Genome Atlas (TCGA) was used to correlate NF-κB signaling and patient survival. The efficacy of cisplatin plus the NF-κB inhibitor dimethylaminoparthenolide (DMAPT) versus cisplatin or DMAPT alone was tested in vitro. Xenografted and immunocompetent MIBC mouse models were studied in vivo. Platinum-naive claudin-low MIBC showed constitutive NF-κB signaling and this was associated with reduced disease-specific survi

SUBMITTER: Gil da Costa RM 

PROVIDER: S-EPMC10701775 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature