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2 in Glioblastoma Multiforme: Implications for Targeted Therapies1 Surgical and Molecular Neuro-oncology Unit, 2 Bioinformatics Group, Intramural Information Technology Program, Division of Intramural Research, and 3 Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Maryland
Requests for reprints: John K. Park, Surgical and Molecular Neuro-oncology Unit, National Institute of Neurological Disorders and Stroke, NIH, Room 2B-1002, 35 Convent Drive, MSC 3706, Bethesda, MD 20892. Phone: 301-402-6935; Fax: 301-480-0099; E-mail: parkjk{at}ninds.nih.gov.
Glioblastoma multiforme is the most common primary malignant brain tumor and despite treatment with surgery, radiation, and chemotherapy, the median survival of patients with glioblastoma multiforme is
1 year. Glioblastoma multiforme explants and cell lines have been reported to overexpress the interleukin-13 receptor
2 subunit (IL13R
2) relative to nonneoplastic brain. Based on this finding, a recombinant cytotoxin composed of IL13 ligand and a truncated form of Pseudomonas aeruginosa exotoxin A (IL13-PE38QQR) was developed for the targeted treatment of glioblastoma multiforme tumors. In a recently completed phase III clinical trial, however, IL13-PE38QQR was found to be no more effective than an existing therapy in prolonging survival. To determine possible explanations for this result, we analyzed the relative expression levels of IL13R
2 in glioblastoma multiforme and nonneoplastic brain specimens using publicly available oligonucleotide microarray databases, quantitative real-time reverse transcription PCR, and immunohistochemical staining. Increased expression of the IL13R
2 gene relative to nonneoplastic brain was observed in 36 of 81 (44%) and 8 of 17 (47%) tumor specimens by microarray and quantitative real-time reverse transcription PCR analyses, respectively. Immunohistochemical staining of tumor specimens showed highly variable expression of IL13R
2 protein both within and across specimens. These data indicate that prescreening of subjects may be of benefit in future trials of IL13R
2 targeting therapies. [Cancer Res 2007;67(17):7983–6]
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