Fig. 1

Outline of how oncogenes and signal transduction inhibitor drugs may contribute to induction and inhibition of tumor angiogenesis, respectively.

Oncogene (e.g., ras) activation can lead to induction of VEGF/VPF, a potent mediator of angiogenesis. VEGF/VPF cannot function as an autocrine growth factor for tumor cells as tumor cells generally lack receptors for VEGF/VPF. In contrast, activated endothelial cells can express high levels of VEGF/VPF, perhaps because of the inductive effect of VEGF/VPF itself. Treatment of the VEGF/VPF-positive tumor cells with a signal transduction inhibitor e.g., a Ras farnesyltransferase inhibitor (FTI), can lead to, among many other changes, a reduction in VEGF/VPF expression. This could in turn lead to a suppressed in vivo angiogenic response. Oncogene activation could also lead to expression of growth factors having both autocrine and paracrine/angiogenesis-promoting functions (such as TGF- α) and/or down-regulation of angiogenesis inhibitory molecules, such as thrombospondin (see text).