PPAR agonists attenuate lenalidomide's anti-myeloma activity in vitro and in vivo.

ABSTRACT: Many patients with multiple myeloma (MM) have comorbidities and are treated with PPAR agonists. Immunomodulatory agents (IMiDs) are the cornerstones for MM therapy. Currently, little is known about how co-administration of PPAR agonists impacts lenalidomide treatment in patients with MM. Here, we determined the effects of PPAR agonists on anti-myeloma activities of lenalidomide in vitro and in a myeloma xenograft mouse model. Genetic overexpression and CRISPR/cas9 knockout experiments were performed to determine the role of CRBN in the PPAR-mediated pathway. A retrospective cohort study was performed to determine the correlation of PPAR expression with the outcomes of patients with MM. PPAR agonists down-regulated CRBN expression and reduced the anti-myeloma efficacy of lenalidomide in vit

SUBMITTER: Sha Y 

PROVIDER: S-EPMC10355274 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature