ABSTRACT
References ........................................................................................................................... 31
The observation that tumor growth can be accompanied by increased vascularity was
reported more than one century ago [for review, see (1)]. In 1939, Ide et al. postulated for
the first time the existence of a tumor-derived blood vessel growth-stimulating factor (2). In
1945, Algire et al. advanced this concept, hypothesizing that rapid tumor growth is crucially
dependent on the development of a neovascular supply (3). In 1971, Folkman (4) proposed
that antiangiogenesis may be a valid strategy to treat human cancer and a search for
regulators of angiogenesis that may also represent therapeutic targets began.
