Table 3.

Cross-validation of target pathways

Tumor microenvironment priority targets	Deregulated metabolism	Evasion of anti-growth signaling	Angiogenesis	Genetic instability	Resistance to cell death	Immune system evasion	Replicative immortality	Sustained proliferative signaling	Tissue invasion and metastasis	Tumor- promoting inflammation
ROS and cellular stress	+ (220)	+/− (221)	+ (222)	0	+/− (223)	+ (224)	+/− (225)	+ (221)	+/− (226)	+ (37)
IL-6 expression, improper dendritic cell maturation and polarization	0	+ (227)	0	0	− (228)	+ (229)	+/0 (230)	− (231)	+ (232,233)	+ (234)
NK cell inhibition	0	− (235)	− (236)	0	+ (237)	+ (238)	0	+ (239)	− (240)	+ (241)
Chronic oxidative stress	+/− (242)	+ (243)	+ (244)	+ (245)	− (246)	0	+ (246)	+ (221)	0	+ (247)
Oxidative stress and IL-6 production	+ (248)	0	+ (249)	0	− (228)	+ (250)	+/− (251,252)	0	0	0

(+): Targets and chemicals those were not only relevant for tumor microenvironment but also relevant for other areas of cancer biology (i.e. pro-carcinogenic). (−): Targets and chemicals that were found to have opposing actions (i.e. anti-carcinogenic). (+/−): Instances where reports on relevant actions in other aspects of cancer biology were mixed (i.e., reports showing both pro-carcinogenic potential and anti-carcinogenic potential). (0): Instances where no literature support was found to document the relevance of a target site or chemical in a particular aspect of cancer biology.