Between 1970 and 1994, cancer claimed the lives of about 500,000 Americans every year. According to the most recent statistics, it is estimated that 1.3 million new cases of cancer will be diagnosed and 555,500 people will die from cancer in the United States in the year 2002. From 1992 to 1998, the incidence of cancer related death was reduced by 1.1%. This modest improvement was related to improved detection and greater therapeutic options. Continued improvement of therapeutic options should further diminish the morbidity and mortality associated with these diseases. Inhibitors of angiogenesis comprise one class of pharmaceuticals with particular promise. This therapeutic class is anticipated to represent a major focus of anti-cancer therapy and indeed by 2006, the market for all products that play a role in angiogenesis is likely to reach $1.75 billion. Although there are multiple opportunities for the development of anti-angiogenic molecules, the most advanced targets are the growth factors. The principal growth factors driving angiogenesis are VEGF, bFGF, and hepatocyte growth factor/scatter factor. Unfortunately these targets play crucial physiological roles and more specific targeting of tumor vasculature is thus required. Japanese researchers have developed a tool for neovasculature-specific drug delivery. This group has used phage-display technology to isolate three distinct phage clones that markedly accumulated in murine tumor xenografts. After the determination of the epitope sequences of these peptides, liposomes were modified with epitope pentapeptides. Liposome modified with one such pentapeptide, APRPG-peptide showed high accumulation in murine tumor xenografts, and APRPG-modified liposome encapsulating adriamycin effectively suppressed experimental tumor growth. Finally, specific binding of APRPG-modified liposome to human umbilical endothelial cells, and that of PRP-containing peptide to angiogenic vessels in human tumors, i.e., islet cell tumor and glioblastoma, were demonstrated. The present study indicates the usefulness of APRPG-peptide as a tool for anti-neovascular therapy, a novel modality of cancer treatment.

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