Ribozyme-mediated inhibition of 801-bp deletion-mutant epidermal growth factor receptor mRNA expression in glioblastoma multiforme.
The epidermal growth factor receptor (HER1/EGFR) is known to be disregulated in a large subgroup of glioblastoma multiforme cases. Disregulation of HER1/EGFR is related to malignant transformation and tumor growth in various human cancers, including malignant glioma. One mechanism that may lead to disregulated HER1/EGFR signaling is the intrinsic alteration of the receptor structure due to mutational changes. The most common mutant form of HER1/EGFR, named variant III (EGFRvIII), results from an 801 bp in-frame deletion in the DNA sequence encoding the extracellular ligand-binding domain. Independent of ligand-binding, EGFRvIII is constitutively activated and beyond external control. Since its cellular expression was shown to relate enhanced tumorigenicity, various therapeutic strategies were developed to target EGFRvIII, including monoclonal antibodies, vaccination therapies and small-molecule tyrosine kinase inhibitors. In this review, we focus on ribozyme-mediated inhibition of EGFRvIII messenger RNA expression as a gene therapeutic approach for EGFRvIII-expressing glioblastoma multiforme.
Karpel-Massler
Georg
G
Department of Neurosurgery, University of Ulm Medical School, Steinhövelstr 9, D-89075 Ulm, Germany. georg.karpel@uniklinik-ulm.de
Wirtz
Christian Rainer
CR
Halatsch
Marc-Eric
ME
D016503:Drug Delivery Systems / Q000379:methods; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D005909:Glioblastoma / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D016337:RNA, Catalytic / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000037:antagonists & inhibitors; D017384:Sequence Deletion
D016337:RNA, Catalytic; D012333:RNA, Messenger; D066246:ErbB Receptors