Antisense Oligonucleotides for Central Nervous System Tumors

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Abstract
The poor prognosis associated with malignant primary brain tumors has led investigators to seek and develop new, innovative treatment modalities. Current adjuvant therapies lack tumor specificity, which can lead to toxic central nervous system side effects. Advances in molecular biology now allow specific gene sequences to be inserted or targeted in the malignant cell genome. Antisense oligodeoxynucleotides represent complementary nucleic acid sequences that can recognize and bind to target genes, resulting in the arrest of deoxyribonucleic acid transcription or the translation of messenger ribonucleic acid. Although the use of antisense oligodeoxynucleotides is still in the experimental stages, these molecules enter cells in tissue culture by simple diffusion or active endocytosis and temporarily inhibit cell proliferation in a time- and dose-dependent fashion. The ability of antisense oligodeoxynucleotides to recognize specific gene sequences and to down-regulate gene expression make them ideal agents for use in targeting oncogenes, such as c-myb, that are expressed in central nervous system neoplasms.