Anti-angiogenic treatment strategies for malignant brain tumors.
The use of angiogenesis inhibitors may offer novel strategies in brain tumor therapy. In contrast to traditional cancer treatments that attack tumor cells directly, angiogenesis inhibitors target at the formation of tumor-feeding blood vessels that provide continuous supply of nutrients and oxygen. With respect to brain tumor therapy, inhibitors of angiogenesis display unique features that are unknown to conventional chemotherapeutic agents. The most important features are independence of the blood-brain barrier, cell type specificity, and reduced resistance. Malignant brain tumors, especially malignant gliomas, are among the most vascularized tumors known. Despite multimodal therapeutic approaches, the prognosis remains dismal. Thus, angiogenesis inhibitors may be highly effective drugs against these tumors. In a clinical setting, they could be applied in the treatment of multiple tumors or postsurgically as an adjuvant therapy to prevent recurrence. This article provides an overview of current anti-angiogenic treatment strategies with emphasis on substances already in clinical trials or candidate substances for clinical trials. The cellular and molecular basis of these substances is reviewed.
Klinik und Poliklinik für Neurochirurgie, Technische Universität Dresden, Germany. matthias.kirsch@mailbox.tu-dresden.de
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D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D043168:Angiostatins; D001932:Brain Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D002986:Clinical Trials as Topic; D003094:Collagen / Q000737:chemistry / Q000627:therapeutic use; D003131:Combined Modality Therapy; D003510:Cyclohexanes; D043169:Endostatins; D016228:Endothelial Growth Factors / Q000037:antagonists & inhibitors / Q000502:physiology; D005231:Fatty Acids, Unsaturated / Q000627:therapeutic use; D005910:Glioma / Q000098:blood supply / Q000188:drug therapy* / Q000601:surgery; D006801:Humans; D016023:Integrins / Q000037:antagonists & inhibitors / Q000502:physiology; D008222:Lymphokines / Q000037:antagonists & inhibitors / Q000502:physiology; D020778:Matrix Metalloproteinase 2 / Q000737:chemistry; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000502:physiology; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000502:physiology; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010446:Peptide Fragments / Q000627:therapeutic use; D010958:Plasminogen / Q000627:therapeutic use; D011506:Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D042787:Receptor, TIE-2; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000502:physiology; D017978:Receptors, Growth Factor / Q000037:antagonists & inhibitors / Q000502:physiology; D042764:Receptors, TIE; D040262:Receptors, Vascular Endothelial Growth Factor; D012717:Sesquiterpenes; D013498:Suramin / Q000627:therapeutic use; D013792:Thalidomide / Q000627:therapeutic use; D019699:Thrombospondins / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D020533:Angiogenesis Inhibitors; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D003510:Cyclohexanes; D043169:Endostatins; D016228:Endothelial Growth Factors; D005231:Fatty Acids, Unsaturated; D016023:Integrins; D008222:Lymphokines; D061965:Matrix Metalloproteinase Inhibitors; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D011506:Proteins; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor; D012717:Sesquiterpenes; D019699:Thrombospondins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D013792:Thalidomide; D013498:Suramin; C026211:fumagillin; D043168:Angiostatins; D010958:Plasminogen; D003094:Collagen; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2; D042764:Receptors, TIE; D040262:Receptors, Vascular Endothelial Growth Factor; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2