title: iNOS: a potential therapeutic target for malignant glioma.
abstract: Glioblastoma is the most aggressive adult primary brain tumor. Although progress has been made in understanding the molecular mechanisms underlying these tumors, current treatments are ineffective. Recent studies have identified iNOS as a critical regulator of glial transformation downstream of EGFRvIII/STAT3 signaling, a key oncogenic pathway in glioblastoma. STAT3 directly binds the promoter of the iNOS gene and thereby stimulates its expression. Importantly, inhibition of iNOS by genetic and pharmacological approaches impedes glial cell proliferation, invasiveness, and tumor growth in vivo. iNOS expression is also elevated in a population of human brain tumor stem cells (BTSCs), and iNOS is required for BTSC proliferation and tumorigenesis. Together, these findings suggest that development of iNOS-targeted therapies may prove valuable in the treatment of glioblastoma. Here, we review our current understanding of iNOS signaling in the regulation of glioblastoma pathogenesis and the potential mechanisms by which iNOS inhibition might suppress the malignant behavior of these devastating tumors.
authors.affiliation: Department of Anatomy and Neurobiology, Washington University School of Medicine, Campus Box 8108, 660 South Euclid Ave, St Louis, MO 63110, USA.
authors.forename: A
authors.initials: A
authors.lastname: Jahani-Asl
authors.forename: A
authors.initials: A
authors.lastname: Bonni
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D066246:ErbB Receptors / Q000378:metabolism; D005910:Glioma / Q000188:drug therapy / Q000201:enzymology*; D006801:Humans; D058990:Molecular Targeted Therapy; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D050796:STAT3 Transcription Factor; C410723:epidermal growth factor receptor VIII; D052247:Nitric Oxide Synthase Type II; D066246:ErbB Receptors