Introduction to special issue: vascular co-option in cancer

Excerpt

Like many great scientific ideas, the concept that solid tumors create new blood vessels that can be targeted as an anticancer strategy was met with skepticism and at times harsh criticism. Dr. Judah Folkman based his pioneering hypothesis on years of observations growing tumors in ex vivo perfused organs and later in the cornea of experimental animals. (The mammalian cornea does not contain blood vessels, so new blood vessels being induced by the presence of tumor-derived pro-angiogenic factors could easily be observed.) Next came studies using cultures of freshly isolated endothelial cells where biochemically purified angiogenesis inducers or inhibitors could be directly tested using in vitro bioassays. Eventually, the identification of potent angiogenic factors from tumor supernatants, for example, VEGF (vascular endothelial growth factor, and many others), informed preclinical models developing pharmacological inhibitors in allografted/xenografted tumors and in genetically engineered mice to formally test the hypothesis that targeting pro-angiogenic pathways could eradicate solid tumors. However, as is now well documented, clinical trials using angiogenesis inhibitors for various cancers have been met with disappointment, and this has spurred the generation of new hypotheses to account for the activation of complex resistance mechanisms that subvert the activity of anti-angiogenic therapies in human cancer patients. …