Molecular therapy for glioblastoma.
Glioblastoma (GB), the relatively frequent and most malignant form of primary brain tumor, is fatal within 1 to 2 years of onset of symptoms, despite conventional therapy. Molecular therapy promises to be an effective and possibly curative treatment. Several molecular strategies have been tested, either in animal models or clinical trials. These include: prodrug activating systems, introduction of tumor suppressor or cell-cycle-related genes, inhibition of growth factors and/or their receptors, inhibition of neovascularization, immunomodulatory maneuvers, oncolytic viruses and inhibition of matrix metalloproteinases. Of special interest for the development of optimal molecular therapy of GB, is the choice of the most efficient and least toxic gene vectors (adenovirus, retrovirus, herpes simplex virus), the route of administration of the therapeutic agent (intratumoral with or without debulking and intracarotid), avoidance of collateral damage to the perineoplastic neuropil and adequate preclinical studies. The ultimate molecular therapy will probably involve the application of multiple simultaneous (combinatorial) therapeutic modalities. The safety and efficiency of these in humans can only be judged by properly controlled therapeutic trials.
Montreal Neurological Institute, 3801 University Street, Montreal, Quebec H3A 2B4, Canada. mcgk@musica.mcgill.ca
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Nalbantoglu
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics / Q000628:therapy*; D002453:Cell Cycle / Q000235:genetics; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D016147:Genes, Tumor Suppressor; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods*; D005822:Genetic Vectors; D005909:Glioblastoma / Q000235:genetics / Q000628:therapy*; D006131:Growth Inhibitors / Q000235:genetics; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D009389:Neovascularization, Pathologic; D011355:Prodrugs / Q000378:metabolism / Q000627:therapeutic use; D014780:Viruses / Q000472:pathogenicity
D000276:Adjuvants, Immunologic; D006131:Growth Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D011355:Prodrugs