Angiozyme: a novel angiogenesis inhibitor.
Several inhibitors of angiogenesis are being developed for the treatment of cancer. One dominant strategy involves disruption of the vascular endothelial growth factor (VEGF) pathway by inhibition of the receptors for VEGF. Inhibition of the VEGF receptor activity can be accomplished using catalytic RNA molecules known as ribozymes, which downregulate VEGF receptor function by specifically cleaving the mRNAs for the primary VEGF receptors, Flt-1 and KDR. Significant inhibition of angiogenesis using ribozymes against both receptors has been demonstrated. In animal tumor models, antitumor effects are most pronounced with the anti-Flt-1 ribozyme known as Angiozyme (Ribozyme Pharmaceuticals, Boulder, CO). Extensive preclinical studies have demonstrated no significant toxicities. Clinical trials of Angiozyme are currently in progress for patients with advanced malignancy. Preliminary results demonstrate Angiozyme to be well tolerated, without significant side effects. Several phase II trials are underway for patients with advanced malignancy to test therapeutic efficacy.
Weng
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Department of Hematology and Oncology, The Cleveland Clinic Foundation, 9500 Euclid Avenue, T-40, Cleveland, OH 44195, USA. wengd@ccf.org
Usman
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D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy*; D016337:RNA, Catalytic / Q000494:pharmacology*; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000187:drug effects* / Q000502:physiology; D017978:Receptors, Growth Factor / Q000187:drug effects* / Q000502:physiology; D040262:Receptors, Vascular Endothelial Growth Factor
D020533:Angiogenesis Inhibitors; C121301:Angiozyme; D016337:RNA, Catalytic; D017978:Receptors, Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor