Table 2.
Cross-validation of target pathways
| Genome instability priority targets | Deregulated metabolism | Evasion of anti- growth signaling | Angiogenesis | Resistance to cell death | Immune system evasion | Replicative immortality | Sustained proliferative signaling | Tissue invasion and metastasis | Tumor-promoting inflammation | Tumor microenvironment |
|---|---|---|---|---|---|---|---|---|---|---|
| DNA repair pathways | + (294) | + (295) | − (296) | + (297) | + (298) | + (299–301) | + (302) | +/− (303–306) | − (307) | 0 |
| Epigenetic pathways: DNA methylation | + (308–310) | + (311) | 0 | +/− (312–314) | + (315) | + (316) | + (317) | + (318–321) | + (322) | 0 |
| Epigenetic pathways: histone acetylation | + (323–325) | + (326) | 0 | − (327–329) | + (330) | + (331) | + (317) | Acetylases: − (332,333); Deacetylases: + (332,334–337) | (338) | 0 |
| Epigenetic pathways: disturbed miRNA binding | + (339,340) | +ent (341) | 0 | +/− (342–344) | + (345) | + (346,347) | + (348) | +/− (349–354) | + (322) | 0 |
| DNA damage signaling: disturbed by redox signaling (NF-κB, Nrf, early growth response (EGR)) | + (355,356) | + (357) | + (358) | − (297) | + (359) | 0 | + (360) | + (361–367) | + (368) | + (369) |
| Mitochondrial function | + (370,371) | + (372) | − (373) | − (374) | + (375,376) | +/− (377–379) | + (380) | Respiration: − (381–383); Bcl- 2: + (384–389) | + (390) | 0 |
| Cell cycle/cell division: spindle defect | +/−; + (391,392) | + (393) | 0 | + (394,395) | + (396) | + (397) | + (398) | 0 | + (399) | 0 |
| Telomere loss | + (400) | − (401) | 0 | − (402–404) | + (405) | − (299) | − (406) | + (407–410) | + (399) | 0 |
Target pathways for genome instability 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 indicated with ‘−’, whereas targets that were found to have promoting actions in a particular hallmark (i.e. carcinogenic) were indicated with ‘+’. In instances where reports on relevant actions in other hallmarks were mixed (i.e. reports showing both pro-carcinogenic potential and anticarcinogenic 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, we documented this as ‘0’.