antiangiogenic steroids in human cancer therapy抗血管新生类固醇在人类癌症治疗.pdfVIP

Advance Access Publication 9 February 2005 eCAM 2005;2(1)49–57 doi:10.1093/ecam/neh066 Review Antiangiogenic Steroids in Human Cancer Therapy Richard J. Pietras and Olga K. Weinberg David Geffen School of Medicine at UCLA, Department of Medicine, Division of Hematology-Oncology, Los Angeles, CA, USA Despite advances in the early detection of tumors and in the use of chemotherapy, radiotherapy and surgery for disease management, the worldwide mortality from human cancer remains unacceptably high. The treatment of cancer may benefit from the introduction of novel therapies derived from natural products. Natural products have served to provide a basis for many of the pharmaceutical agents in current use in cancer therapy. Emerging research indicates that progressive growth and spread of many solid tumors depends, in part, on the formation of an adequate blood supply, and this process of tumor- associated angiogenesis is reported to have prognostic significance in several human cancers. This review focuses on the potential application in antitumor therapy of naturally-occurring steroids that target tumor-associated angiogenesis. Squalamine, a 7,24 dihydroxylated 24-sulfated cholestane steroid conjugated to a spermidine at position C-3, is known to have strong antiangiogenic activity in vitro, and it significantly disrupts tumor