Table 1.
Effects of the selected targets for anti-angiogenic cancer therapy on other cancer “hallmarks”.
| Other cancer hallmarks | Angiogenesis targets |
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| (Inhibit) endothelial cell migra-tion/tip cell formation | (Reduce) structural abnormalities of tumor vessels | (Reduce) hypoxia | (Inhibit) lymphangiogenesis | (Reduce) elevated interstitial fluid pressure | (Reverse) poor perfusion | (Norma-ize) disrupted circadian rhythms | (Suppress) tumor promoting inflammation | (De-activate) tumor promoting fibroblasts | (Normalize) tumor cell metabolism/acidosis | |
| Genetic instability | 0 | 0 | + [239] | 0 | 0 | 0 | + [240] | 0 | 0 | + [241] |
| Sustained proliferative signaling | 0 | 0 | + [242] | +/− [243], [244] | + [245], [246] | 0 | + [247], [248] | 0 | + [249], [250] | 0 |
| Tumor-promoting inflammation | + [251] | + [252] | + [253], [254] | 0 | + [255] | + [252], [256] | + [257] | NA | + [258] | + [259] |
| Evasion of anti-growth signaling | + [260] | 0 | +/− [261], [262] | 0 | + [246] | +/− [263], [264], [265] | +/− [266], [267] | + [268] | + [269], [270] | + [271], [272] |
| Resistance to apoptosis | 0 | + [273] | + [274] | 0 | + [275] | + [276] | + [277] | + [278] | + [279] | + [280] |
| Replicative immortality | 0 | 0 | + [281], [282], [283] | 0 | 0 | 0 | +/− [284], [285] | 0 | 0 | 0 |
| Dysregulated metabolism | + [286] | + [287], [288] | + [289], [290], [291] | 0 | + [292] | + [293], [294] | + [295] | 0 | + [296] | + [297] |
| Immune system evasion | + [298] | + [299], [300] | + [301], [302] | + [303] | + [304], [305] | + [306] | + [307] | + [308], [309] | + [310], [311] | + [312], [313] |
| Invasion and metastasis | + [287] | + [15], [314] | + [315] | + [316] | + [317], [318], [319] | + [320] | + [321], [322], [323] | + [324] | + [323] | + [325], [326] |
| Interactions in the tumor micro-environment | + [260] | + [327] | + [328] | + [329] | + [330] | + [327] | + [331] | + [332] | + [333], [334] | + [335] |
Our 10 identified targets of anti-angiogenesis therapy are presented in the top row. 10 other cancer “hallmarks” are listed in the column to the left. Positive interactions (i.e. if the anti-angiogenesis target could also be a target for the indicated “hallmark”) are denoted “+”, controversial interactions (i.e. if the anti-angiogenesis target could both promote and inhibit the indicated “hallmark”) are denoted “+/−” and no interaction (i.e. if we have not been able to find any interaction between the anti-angiogenesis target and the indicated “hallmark”) is denoted “0”.