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Antisense
Oligodeoxynucleotide Technology: Potential Use for the Treatment of Malignant
Brain Tumors
Engelhard HH
Division of Neurological Surgery, Northwestern University Medical
School, Chicago, Illinois 60611, USA.
Background. Antisense oligodeoxynucleotides (ODNs) have been proposed as
a new therapy for patients with cancer, including malignant brain tumors.
Antisense ODNs are taken up by tumor cells and selectively block gene
expression.
Use of ODNs for brain tumors is attractive due to their theoretical specificity,
relative ease of production and, to date, paucity of reported adverse
effects.
This article presents current information regarding antisense ODNs and their
possible future use for the treatment of brain tumors.
Methods.
The available published experimental and clinical information regarding
antisense ODN treatment of glioblastoma cells and administration into the
central nervous system (CNS) was reviewed.
Other clinically relevant information pertaining to the molecular biology of
antisense ODNs was also collected and summarized.
Results.
Targets for antisense ODN therapy in malignant glioma cells have included c-myc,
c-myb, c-sis, c-erb B, CD44, p34cdc2, bFGF, PDGF, TGF-beta, IGF-1, PKC-alpha
tumor necrosis factor, urokinase, and S100beta protein.
Few in vivo studies of ODN treatment of brain tumors have yet been
reported.
Systemically administered ODNs enter the brain only in extremely small
quantities; therefore, microinfusion into the brain has been recommended.
Conclusions.
Antisense ODNs have been used successfully to block glioblastoma gene expression
in vitro and expression of multiple genes within the CNS of experimental
animals.
Upcoming clinical trials will address the safety of antisense ODN use against
malignant brain tumors.
PMID: 10761027 [PubMed - as supplied by publisher]
Source: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10761027&dopt=Abstract
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