Title: Nucleic Acid-based Technologies in Therapy of Malignant Gliomas
Volume: 12
Issue: 11
Author(s): Monika Piwecka, Katarzyna Rolle, Eliza Wyszko, Ryszard Zukiel, Stanislaw Nowak, Miroslawa Z. Barciszewska and Jan. Barciszewski
Affiliation:
Keywords:
Glioblastoma multiforme, GBM, brain tumors, malignant gliomas, brain tumor therapy, RNA interference, Tenascin-C, ATN-RNA, antisense oligonucleotides, nucleic acid-based therapeutic technologies, cellular polymorphism, vascular thrombosis, tumor cells, heterogeneous nature, actin-binding molecules
Abstract: Malignant gliomas are the deadliest brain tumors, which are characterized by highly invasive growth, a rampant genetic instability and intense resistance to apoptosis. Such an aggressive behavior of malignant gliomas is reflected in the resistance to chemo- and radiotherapy and weak prognosis in spite of cytoreduction through surgery. Brain tumors preferentially express a number of specific protein and RNA markers, that may be exploited as potential therapeutic targets in design of the new treatment modalities based on nucleic acids. For almost three decades, a possibility to apply DNA and RNA molecules as anticancer therapeutics have been studied. A variety of antisense oligonucleotides, ribozymes, DNAzymes, and aptamers can be designed to trigger the sequence-specific inhibition of particular mRNA of interest. RNA interference (RNAi) is the latest and the most promising technique in the long line of nucleic acid-based therapeutic technologies. Recently, we designed and implemented the experimental therapy of patients suffering from malignant brain tumors based on application of double-stranded RNA (dsRNA) specific for tenascin-C (TN-C) mRNA. That therapeutic agent, called ATN-RNA, induces RNAi pathway to inhibit the synthesis of TN-C, the extracellular matrix protein which is highly overexpressed in brain tumor tissue. In the chapter specific problems of application of nucleic acid-based technologies in glioma tumors treatment will be discussed.
