The role of vascular endothelial growth factor (VEGF) in AIDS-related Kaposi's sarcoma.
Kaposi's sarcoma (KS) is the most common neoplasm associated with human immunodeficiency virus-1 (HIV-1) infection. KS involves the skin and mucous membranes as well as other organs and can lead to tumor-associated edema and ulcerations. Despite therapy with highly active antiviral agents, most patients with HIV-1-related KS eventually develop disseminated disease. In the treatment of KS, a strong rationale exists for the use of agents that inhibit vascular endothelial growth factor (VEGF). Angiogenesis appears to be an important feature of this disease, and recent experimental studies have demonstrated the role of VEGF and its receptors in the pathogenesis of KS. Thus, therapeutic agents that target the VEGF pathway may be an effective strategy in reducing the tumor growth and edema associated with KS. Phase I study results with SU5416, a synthetic low molecular-weight inhibitor of the VEGF-Flk-1/KDR receptor tyrosine kinase, demonstrate that this agent is well tolerated. Preliminary results show that in a majority of patients with autoimmune deficiency syndrome (AIDS)-related disease, SU5416 clearly has biological activity (it flattens, shrinks, or dissolves lesions and reduces or resolves edema) or stabilizes the disease. Angiogenesis inhibition with SU5416 is a promising therapeutic approach in treating patients with KS, and further clinical evaluation is currently under way.
Arastéh
K
K
Auguste-Viktoria-Krankenhaus, Berlin, Germany. arasteh@avk.b.shuttle.de
Hannah
A
A
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy / Q000503:physiopathology*; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use; D016228:Endothelial Growth Factors / Q000037:antagonists & inhibitors / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D015497:HIV-1; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D008222:Lymphokines / Q000037:antagonists & inhibitors / Q000502:physiology*; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011758:Pyrroles / Q000627:therapeutic use; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D017978:Receptors, Growth Factor / Q000037:antagonists & inhibitors / Q000502:physiology; D011975:Receptors, Mitogen / Q000037:antagonists & inhibitors / Q000502:physiology; D040262:Receptors, Vascular Endothelial Growth Factor; D012514:Sarcoma, Kaposi / Q000098:blood supply / Q000188:drug therapy / Q000503:physiopathology*; D012878:Skin Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000503:physiopathology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D020533:Angiogenesis Inhibitors; D000998:Antiviral Agents; D016228:Endothelial Growth Factors; D004791:Enzyme Inhibitors; D007211:Indoles; D008222:Lymphokines; D020033:Protein Isoforms; D011758:Pyrroles; D017978:Receptors, Growth Factor; D011975:Receptors, Mitogen; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C116890:Semaxinib; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor