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Potential of gene therapy for brain tumors
Paula Y.P. Lam and Xandra O. Breakefield
Molecular Neurogenetics Unit, Massachusetts General Hospital,
and Department of Neurology and Neuroscience Program, Harvard Medical School,
Boston, MA 02114, USA [P.Y.P.L., X.O.B.] and National Cancer Centre, Division of
Molecular and Cellular Research, National Cancer Centre, 169610 Singapore
[P.Y.P.L.].
Correspondence to X.O.B. at: Massachusetts General Hospital East,
Deptartment of Molecular Neurogenetics, 13th Street, Building 149,
Charlestown, MA 02129, USA. Tel: +1 617 726 5728; Fax: +1 617 724
1537; Email: breakefield@helix.mgh.harvard.edu.
Received 12 January 2001 ; Revised and Accepted 26 January 2001.
Brain tumors comprise a broad spectrum of biological and clinical entities
making it unlikely for any single therapeutic approach to be
universally applicable.
In particular, malignant glioblastoma multiforme
have defied all current therapeutic modalities.
Gene therapy offers
the potential to augment current neurosurgical, radiation and drug
treatments with little increase in morbidity.
Many therapeutic
transgenes have shown efficacy in experimental models, including
generation of toxic compounds, enzymatic activation of pro-drugs,
expression of tumor suppressor or apoptotic proteins, inhibition of
angiogenesis and enhancement of immune responses to tumor antigens.
Vectors have been used as gene delivery vehicles and as cytotoxic
agents in their own right by selective replication and lysis of tumor
cells, thereby also generating vectors on-site.
Brain tumors appear
to offer some ‘Achilles’ heels’ in that they are usually
contained within the brain and represent a unique dividing cell
population there.
However, the heterogeneous and invasive
characteristics of these tumor cells, as well as sequestration of
tumor antigens within a relatively immune privileged location present
serious problems for effective therapy.
This review will focus on
current transgene/vector strategies, including novel therapeutic
genes, combinational therapies and new delivery modalities, the
latter of which appears to be the rate limiting factor for gene
therapy of brain tumors in humans.
© 2001 Oxford University Press
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