Tumor Suppression Through Angiogenesis Inhibition

In the early 1970s, Judah Folkman first proposed the hypothesis that tumor growth was dependent on the recruitment of blood vessels, a process called angiogenesis, and that angiogenesis was both an important stage in tumor development and a promising therapeutic target. Based on his observations as a surgeon, he also postulated the existence of circulating molecules that could inhibit this process, so-called angiogenesis inhibitors. The ideas of Folkman and other pioneers (reviewed in ref. 1 ), received skeptically by the scientific community at the time, have become one of the central dogmas of cancer research. A PubMed search for the terms “tumor” and “angiogenesis” turns up 508 papers between 1981 and 1991, and 4604 between 1991 and 2001, a 9-fold increase (compared to a 1.3-fold increase in the word “tumor” alone over the same period). Nearly a thousand such papers have been published in the past year. In addition to the angiogenesis inhibitors that Folkman’s own group isolated, upwards of 40 biological inhibitors of angiogenesis have been discovered in recent years, as well as numerous pharmacologic compounds with similar activities. Many of these molecules are currently undergoing clinical trials as anticancer drugs (reviewed in ref. 2 ).