MEK Inhibition Suppresses Growth of Atypical Teratoid/Rhabdoid Tumors. Issue 7 (29th May 2020)

• Record Type: Journal Article
• Authors: Shahab, Shubin; Rubens, Jeffrey; Kaur, Harpreet; Sweeney, Heather; Eberhart, Charles G; Raabe, Eric H
• Is Part Of: Journal of neuropathology and experimental neurology. Volume 79:Issue 7(2020)
• Page Start: 746
• Page End: 753
• Publication Date: 2020-05-29
• Subjects: INI1 -- Malignant rhabdoid tumor -- MEK162 -- Pediatric brain tumor -- RAS; Neurology -- Diseases -- Periodicals; Neurology -- Diseases -- Physiopathology -- Periodicals; 616.8047
• DOI: 10.1093/jnen/nlaa042
• Languages: English
• ISSNs: 0022-3069

Abstract

Abstract: Atypical teratoid/rhabdoid (AT/RT) tumors are the most common malignant brain tumor of infancy and have a poor prognosis. We have previously identified very high expression of LIN28A and/or LIN28B in AT/RT tumors and showed that AT/RT have corresponding increased expression of the mitogen-activated protein (MAP) kinase pathway. Binimetinib is a novel inhibitor of mitogen-activated protein kinase (MAP2K1 or MEK), and is currently in pediatric phase II clinical trials for low-grade glioma. We hypothesized that binimetinib would inhibit growth of AT/RT cells by suppressing the MAP kinase pathway. Binimetinib inhibited AT/RT growth at nanomolar concentrations. Binimetinib decreased cell proliferation and induced apoptosis in AT/RT cells and significantly reduced AT/RT tumor growth in flank xenografts. Our data suggest that MAP kinase pathway inhibition could offer a potential avenue for treating these highly aggressive tumors.