Table 2.
Cross-validation of target pathways
| Target pathways | Deregulated metabolism | Evasion of antigrowth signaling | Angiogenesis | Genetic instability | Immune system evasion | Replicative immortality | Sustained proliferative signaling | Tissue invasion and metastasis | Tumor promoting inflammation | Tumor microenvironment |
|---|---|---|---|---|---|---|---|---|---|---|
| Binding to ERα | +(100) | −(196) | 0 | 0 | 0 | +(197,198) | +(199–201) | +/−(101– 103,202,203) | +(204,205) | +(206) |
| P53 | +(207) | −(208) | −(209) | −(210,211) | +(212,213) | +(214–217) | −(218) | −(219–222) | +(223–225) | +(226) |
| ErbB-2/HER-2 tyrosine kinase | 0 | −(227) | 0 | +(138,228) | 0 | +(229,230) | +(216) | +(231–234) | +(235,236) | +(237) |
| ERK/MAPK | +(196,238,239) | +(240,241) | +(242) | −(243,244) | −(245,246) | +(247) | +(154) | +(248–252) | +(253) | +(254) |
| MAP kinase | +(255) | +(240,241,256) | +(257) | +(138,258) | +/−(246,259) | +(260–262) | +(138) | +(248–250) | +(263,264) | +(254) |
| P16/p53 | 0 | 0 | −(265) | −(266,267) | +(268,269) | +(214,270) | − (271) | − (267,272–275) | +(276) | +(277) |
| Bcl-2/p53 | 0 | +/−(278–287) | +(288,289) | −(290) | +(291–293) | +(229,294) | −(271) | +(289,295,296) | +(297) | +(298) |
| PPAR-α | +(299,300) | −(301–303) | −(304) | 0 | 0 | −(301) | +/−(167,192) | 0 | +(305,306) | +(307) |
| GJIC | 0 | 0 | 0 | 0 | 0 | 0 | −(308) | +/−(309–311) | +(312) | +(313) |
| Hypersecretion of LH by gonadotroph cells in pituitary gland | 0 | 0 | 0 | 0 | 0 | 0 | −(314) | +(315,316) | +(317,318) | 0 |
Target pathways resistance to cell death were cross-validated for effects in other cancer hallmark pathways. Targets that were found to have opposing actions in a particular hallmark (i.e. anticarcinogenic) 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 anticarcinogenic potential), the symbols ‘ +/−’ were 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, we denoted using ‘0’.