Table 2.
Cross-validation of target pathways
| Priority targets | Sustained proliferative signalling | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Deregulated metabolism | Evasion of anti-growth signalling | Angiogenesis | Genetic instability | Resistance to cell death | Replicative immortality | Tissue invasion and metastasis | Tumor promoting inflammation | Tumor microenvironment | |
| H-Ras | ± (139,140) | + (141,142) | + (143) | + (144) | ± (145,146) | − (147) | + (148) | + (149,150) | + (151) |
| Jun/Fos/AP1 | ± (152,153) | − (154–157) | 0 | + (158,159) | ± (160,161) | ± (162,163) | + (164) | + (165,166) | + (151) |
| Cyclin D, IL8, CXCL | ± (167–170) | 0 | + (171) | + (172) | 0 | ± (173,174) | + (175) | + (176,177) | 0 |
| PPAR | + (178) | + (179) | − (180) | 0 | − (181,182) | + (183–185) | + (186) | + (187) | 0 |
| AhR | + (188) | + (189) | + (190) | + (191) | ± (192–194) | + (195,196) | ± (197,198) | + (199) | + (200) |
| EGF receptor | + (201) | 0 | + (202) | + (203) | ± (204,205) | + (206) | + (207) | + (208) | 0 |
| Steroid hormone receptors | + (209) | 0 | 0 | + (210) | 0 | ± (211–213) | + (214) | + (215,216) | + (217) |
Target pathways sustained proliferative signalling were cross-validated for effects in other cancer hallmark pathways. Targets that were found to have opposing actions in a particular hallmark (i.e. anti-carcinogenic) were denoted using ‘−’, whereas targets that were found to have promoting actions in a particular hallmark (i.e. carcinogenic) were denoted using ‘+’. In instances where reports on relevant actions in other hallmarks were mixed (i.e. reports showing both pro-carcinogenic potential and anti-carcinogenic potential), the symbol ‘±’ was used. Finally, in instances where no literature support was found to document the relevance of a target in a particular aspect of cancer’s biology were denoted ‘0’.