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Therapeutic Ribonucleic Acids in Brain Tumors pp 425–451Cite as

Brain Tumor Therapy with Antisense Oligonucleotides

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Abstract

Antisense oligonucleotides (AON), short oligonucleotides of DNA, which selectively bind to complementary mRNA inside the cytoplasm, can specifically block genes and production of designated proteins. The use of AP12009 against TGF-β2 has been the most frequently studied antisense therapy for brain tumors so far. Further oncogenes e.g. c-Met, RAS or Bcl-2, the growth factors VEGF, EGFR, IGF-1 or the enzyme telomerase have been suggested as such targets. Other antisense strategies deal with an immunological approach such as the use of AON with CpG motifs. Systemic therapy with AON is limited by its degradation in plasma and, in case of brain tumors, by the blood–brain-barrier. Many studies approach these problems with a construction of modified AON, with coupling to liposomes or nanoparticles or with direct administration into the brain via convection-enhanced delivery. All antisense strategies are promising options, but currently and in the foreseeable future there is no cure for malignant glioma by a single therapeutical regime. Possibly a combination of several strategies may be a more effective approach for these cruel tumors.

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Abbreviations

AON:

Antisense oligonucleotides

BBB:

Blood–brain-barrier

CED:

Convection-enhanced delivery

CNS:

Central nervous system

CSF:

Cerebro-spinal fluid

EGFR:

Epidermal growth factor receptor

IGF-I:

Insulin-like growth factor type I

PKC-\alpha:

Protein kinase C alpha

TGF:

Transforming growth factor

VEGF:

Vascular endothelial growth factor

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Authors and Affiliations

  1. Department of Neurosurgery, Otto-von-Guericke University, Leipziger Str. 44, 39120, Magdeburg, Germany

    Thomas Schneider

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Editors and Affiliations

  1. Inst. Chemie und Biochemie, FU Berlin, Thielallee 63, Berlin, 14195, Germany

    Volker A. Erdmann

  2. Inst. Neuropathologie, Universitätsklinikum Düsseldorf, Moorenstr. 5, Düsseldorf, 40225, Germany

    Guido Reifenberger

  3. Inst. Bioorganic Chemistry, PAN Poznan, ul. Z. Noskowskiego 12/14, Poznan, 61-704, Poland

    Jan Barciszewski

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Schneider, T. (2009). Brain Tumor Therapy with Antisense Oligonucleotides. In: Erdmann, V., Reifenberger, G., Barciszewski, J. (eds) Therapeutic Ribonucleic Acids in Brain Tumors. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-00475-9_19

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