Angiogenesis inhibitors: current strategies and future prospects.
Angiogenesis has become an attractive target for drug therapy because of its key role in tumor growth. An extensive array of compounds is currently in preclinical development, with many now entering the clinic and/or achieving approval from the US Food and Drug Administration. Several regulatory and signaling molecules governing angiogenesis are of interest, including growth factors (eg, vascular endothelial growth factor, platelet-derived growth factor, fibroblast growth factor, and epidermal growth factor), receptor tyrosine kinases, and transcription factors such as hypoxia inducible factor, as well as molecules involved in mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) signaling. Pharmacologic agents have been identified that target these pathways, yet for some agents (notably thalidomide), an understanding of the specific mechanisms of antitumor action has proved elusive. The following review describes key molecular mechanisms and novel therapies that are on the horizon for antiangiogenic tumor therapy.
Cook
Kristina M
KM
Molecular Pharmacology Section, Medical Oncology Branch and Affiliates, National Cancer Institute, National Institutes of Health, 10 Center Drive, 9000 Rockville Pike, Bethesda, MD 20892, USA.
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William D
WD
D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D051792:Basic Helix-Loop-Helix Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D002471:Cell Transformation, Neoplastic; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011485:Protein Binding / Q000187:drug effects; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D051880:Receptors, Notch / Q000037:antagonists & inhibitors / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D013879:Thioredoxins / Q000037:antagonists & inhibitors
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D051792:Basic Helix-Loop-Helix Proteins; D051231:Farnesyltranstransferase; D018841:HSP90 Heat-Shock Proteins; D047908:Intracellular Signaling Peptides and Proteins; D019384:Nucleic Acid Synthesis Inhibitors; D020794:Receptor Protein-Tyrosine Kinases; D051880:Receptors, Notch; D013879:Thioredoxins