Inhibition of Y-box binding protein-1 slows the growth of glioblastoma multiforme and sensitizes to temozolomide independent O-methylguanine-DNA methyltransferase

Glioblastoma multiforme (GBM) is an aggressive type of brain tumor where <3% of newly diagnosed cases in the patients will survive >5 years. In adults, GBM is the most common type of brain tumor. It is rarer in children, where it constitutes ∼15% of all brain tumors diagnosed. These tumors are often invasive, making surgical resection difficult. Further, they can be refractory to current therapies such as temozolomide. The current dogma is that temozolomide resistance rests on the expression of O-methylguanine-DNA methyltransferase (MGMT) because it cleaves methylated DNA adducts formed by the drug. Our laboratory recently reported that another drug resistance gene known as the Y-box binding protein-1 (YB-1) is highly expressed in primary GBM but eceived 6/2/09; revised 9/24/09; accepted 10/21/09; published nlineFirst 12/8/09. rant support: Canadian Cancer Research Society (S.E. Dunn and . Jabado), Canadian Institute for Health Research and C17 Research etwork (S.E. Dunn), and Michael Cuccione Foundation (S.E. Dunn and . Lee). he costs of publication of this article were defrayed in part by the ayment of page charges. This article must therefore be hereby marked dvertisement in accordance with 18 U.S.C. Section 1734 solely to dicate this fact. ote: Supplementary material for this article is available at Molecular ancer Therapeutics Online (http://mct.aacrjournals.org/). . Gao and A. Fotovati contributed equally to this work. equests for reprints: Sandra E. Dunn, Departments of Pediatrics, xperimental Medicine and Medical Genetics, Child and Family Research stitute, University of British Columbia, 950 West 28th Avenue, ancouver, British Columbia, Canada V5Z 4H4. Phone: 604-875-2000, xt. 6015; Fax: 604-875-3120. E-mail: [email protected] opyright © 2009 American Association for Cancer Research. R O