Pharmacologic Inhibition of EIF4A Blocks NRF2 Synthesis to Prevent Osteosarcoma Metastasis

Michael Lizardo, MS, PhD, a staff scientist in the Poul Sorensen laboratory at BC Cancer Agency, joins us on OsteoBites to discuss how the pharmacologic inhibition of EIF4A blocks NRF2 synthesis to prevent osteosarcoma metastasis.Dr. Lizardo shares his lab's recent findings in Clinical Cancer Research on how targeting the dysregulated mRNA translation factor eukaryotic initiation factor 4A (EIF4A), via pharmacological inhibitors, prevents the protein synthesis of nuclear factor erythroid 2–related factor 2 (NRF2), which is a cytoprotective protein metastatic OS cells require to successfully colonize the harsh microenvironment of the lung. He also discusses how the EIF4A1 inhibitor, CR-1-31B, and a related clinical-grade compound (Zotatifin) prevent OS cell adaptation to oxidative stress (a major stressor in the lung) in 2D and 3D cell culture models, as well as ex vivo lung organotypic cultures. Moreover, he discusses how drug treatment can inhibit lung metastasis and prolong the survival of animal subjects in pre-clinical mouse models of metastatic OS.