Targeting Angiogenic Factors Contributing to Etiology and Progression of Human Ovarian Cancer
Abstract
Development of human ovarian cancer depends, in part, on formation of an adequate blood supply. Tumor angiogenesis is essential for cancer growth, and vascular endothelial growth factor (VEGF) is critical in stimulating growth of vascular endothelial cells. VEGF is produced by ovarian cancers, and VEGF secretion is markedly increased in ovarian cancers with HER-2 oncogene overexpression. Herceptin, an antibody to HER-2 receptor, has direct antitumor effects, but the antireceptor antibody also elicits a significant reduction in VEGF secretion from ovarian cancer cells,and, thereby, retards ovarian tumor-associated angiogenesis. More complete suppression of angiogenesis may be elicited by treatments that synergistically suppress blood vessel proliferation, such as squalamine, an angiostatic steroid approved by the FDA as an orphan drug candidate for treatment of ovarian cancer. In studies with human ovarian cancer cells in vivo, squalamine elicits antitumor activity by suppressing the angiogenic action of several vascular growth factors including VEGF, an effect that may be due to squalamine-induced blockade of MAP kinase activation. Ongoing work evaluates the efficacy of squalamine alone and combined with other antitumor therapies, including cisplatin, carboplatin and Herceptin, in suppressing growth of human ovarian cancers with and without HER-2 oncogene overexpression.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2002
- Accession Number
- ADA412139
Entities
People
- Richard J. Pietras
Organizations
- University of California, Los Angeles