Introduction 1 1 Fig. 1 Schematic NF-κB pathway. In the canonical activation pathway, NF-κB (often the dimer composed of p50/p65) is sequestered by its main inhibitor IκB-α. Upon stimulation, cell surface receptors activate IKK complex, which then phosphorylate IκB-α. These phosphorylations lead to its degradation by the proteasome and the entry of NF-κB in the nucleus, which turns on target genes  2 4 3 5 6 7 8 9 10 11 12 14 15 16 NF-κB in ongoing angiogenesis 17 18 19 20 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 A role for NF-κB in angiostatic therapy? 29 43 44 45 45 46 48 49 50 51 52 53 54 In conclusion, while in tumor cells NF-κB is mostly described as an oncogenic factor, up-regulation of NF-κB in endothelial cells is associated with angiostatic activity. It might therefore be warranted to revisit anti-cancer therapies based on inhibition of NF-κB activity for effects on angiogenesis. An indirect anti-tumor activity of NF-κB through circumvention of endothelial cell anergy 55 56 57 58 59 60 61 62 44 63 Where to go from here? 2 Fig. 2 Model of the dual role of NF-κB in tumorigenesis. In tumor cells, activation of NF-κB leads to tumor growth by both direct and indirect mechanisms. The direct mechanisms involve expression of anti-apoptotic and pro-proliferative molecules while the indirect mechanism involves promotion of angiogenesis. In endothelial cells, activation of NF-κB can block tumor progression by both, angiostatic activity, via the production of pro-apoptotic molecules and by improvement of immune response via expression of adhesion molecules