Although this transcription factor activates tumor-suppressive pathways at early oncogenesis, upon disease progression unbalanced E2F1 activity is rewired to deregulated cancer networks that underlie hallmarks of metastatic progression such as resistance to apoptosis, chemoresistance [3, 8], neoangiogenesis [9], extravasation [6], EMT [10, 11], metabolic reprogramming [12], and genomic instability [13]. The gene discussed is E2F1; the disease is cancer.