Table 1.

Cross-validation of anti-growth signaling or tumor suppressor pathways with other hallmarks of cancer

Priority targets for evasion of anti-growth signaling	The Rb pathway: Inactivation of E2F by down-regulation of hyper-phosphorylated Rb or inactivating CDKs.	The p53 pathway: Activation through up-regulation of wild type p53	PTEN pathway: Activation by inhibiting PI3K-AKT	The Hippo pathway: Activation by inhibiting YAP/TEAD activity	Induction of GDF 15 through p53 activation	Activation of tumor suppressor ARID1A	Blocking NOTCH pathway in association with tumor suppressors	Inhibition of IGF-1R to restore tumor suppressor pathways
Other cancer hallmarks
Genomic instability	+ [309]	+ [310]	+ [311, 312]	0	− [313]	+ [314]	0	0
Sustained proliferative signaling	0	+ [315, 316]	+ [317–320]	+ [321–323]	0	+ [324]	+ [325]	+ [326–330]
Tumor promoting inflammation	0 [331]	+ [332–335]	+ [336, 337]	0	0	0	+ [338]	+ [339, 340]
Resistance to apoptosis	+ [341]	+ [342]	+ [343]	+ [344]	+ [345]	+	+ [346]	+ [347]
Replicative immortality	+ [348]	+ [349, 350]	+ [351]	0	0	0	+ [352]	+ [353, 354]
Dysregulated metabolism	+ [355]	+ [356–359]	+ [360–362]	+ [363]	0	+ [364]	+ [365]	0
Immune system evasion	0	+ [366]	+ [367]	0	0	0	0	0
Angiogenesis	+ [368]	0 [369]	+ [370]	0	+ [371]	0	− [372]	−[373]
Invasion and metastasis	+ [374, 375]	+ [376]	+ [377]	+ [323, 378]	+ [379]	− [123, 380]	+ [381, 382]	− [383, 384]
Interactions in the tumor microenvironment	− [385, 386]	+ [387, 388]	+ [389, 390]	+ [391]	+ [392]	0	+ [393]	+ [330]

Foot notes: “+” indicates complementary; “−” contrary and “0” no known relationship