Table 2.

Involvement of the cellular pathways promoting replicative immortality in the development of the hallmarks of cancer identified by Hanahan et al. (165)

Replicative immortality priority targets	Deregulated metabolism	Evasion of antigrowth signaling	Angiogenesis	Genetic instability	Resistance to cell death	Immune system evasion	Sustained proliferative signaling	Tissue invasion and metastasis	Tumor promoting inflammation	Tumor micro- environment
Telomerase activation	+ (266)	+ (266)	+ (266)	+ (266)	+ (267)	+ (266)	+ (266)	+ (266)	+ (266))	− (268)
P53 inactivation	+ (269)	+ (270)	+ (271)	+ (272)	+ (273)	+ (274)	+ (275)	+ (276)	+ (277)	+ (278)
pRb inactivation	+ (279)	+ (280)	+ (281)	+ (282)	+ (283)	0	+ (284)	+ (285)	+ (286)	+ (287)
mTOR inactivation	+ (288)	+ (289)	− (290)	+ (291)	− (292)	− (293)	− (288)	− (294	− (295)	+/− (278)

Targets that were found to have opposing actions in a particular hallmark (i.e. anticarcinogenic) were denoted using ‘−’, while targets that were found to have promoting actions in a particular hallmark (i.e. pro-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, were denoted using ‘0’.