We have developed a novel substance called superfibronectin (sFN) that prevents the spread of cancer through the blood stream. It also prevents cancerous tumors from building up their own blood circulation. Like all normal tissues, cancers cannot survive without being nurtured by the blood. Indeed, strangulation of cancer by interfering with its blood supply has become one of the most promising experimental cancer treatments. sFN is particularly effective in suppressing the growth and spread of experimental ovarian cancer in mice. Unlike most of the established treatments for cancer, sFN has proven to be quite nontoxic in these animal experiments. Thus, further understanding of how sFN works will be important. To provide such understanding is one goal of this proposal. Moreover, it turns out that the ability of sFN to prevent the growth of tumor blood vessels closely resembles the activities of several other recently discovered compounds, some of which are being tested in cancer patients, because animal experiments have shown them to have remarkable anticancer activities with few side effects. However, one major limitation in their use is that it is not known how they work, meaning the treatments have to be based on trial and error rather than deliberate design. Based on the similarities between sFN and these other inhibitors of blood vessel growth, we have formulated a hypothesis on a common mechanism of action for these substances and propose in this Idea Award application to test that hypothesis. This information may further improve the already highly promising new way of treating cancers by restricting their blood supply. In this manner, studies on the effects of sFN on ovarian cancer may have a wider significance to the treatment of various other types of cancers.