PI-88: a novel inhibitor of angiogenesis

Abstract

Growth factors that stimulate angiogenesis are vital in tumor development and maintenance. Inhibitors of angiogenesis are emerging as key elements in anticancer treatments, and now antibodies and small molecule kinase inhibitors are approved in the treatment of a variety of solid tumors. These have shown modest but statistically significant benefit in colon, breast and lung cancers. PI-88 has a novel mechanism of action compared to the drugs on the market today. By inhibiting heparanase, PI-88 blocks angiogenesis on several different cellular and biological levels. Promising results from Phase I/II trials are being seen with PI-88 in a variety of tumor types including melanoma and hepatocellular carcinoma. However, the development of antibody-induced thrombocytopenia has limited its use in some patients.

Keywords::

• angiogenesis
• heparanase
• heparan sulfate
• hepatocellular carcinoma
• melanoma
• lung cancer
• PI-88
• prostate cancer
• vascular–endothelial growth factors

Acknowledgments

The authors thank Keith Dredge, the preclinical manager at Progen, for providing Figure 3A and B.

Notes