The Role of Vascular Endothelial Growth Factor in Restenosis

Abstract

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 treat- ment 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 demon- strated the role of VEGF and its receptors in the patho- genesis 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 tyro- sine kinase, demonstrate that this agent is well tolerated. Preliminary results show that in a majority of patients with autoimmune deficiency syndrome (AIDS)-related dis- ease, 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 treat- ing patients with KS, and further clinical evaluation is cur- rently under way. The Oncologist 2000;5(suppl 1):28-31