Our study contributes at three distinct levels: (i) new data—the identification of five recurrent binding motifs and 128 candidate TFs regulating 622 cancer driver genes; (ii) new analysis—the reconstruction of an interaction network that revealed an emergent MYC-centered hub of eleven TFs; and (iii) new concept—the Eternity Triangle, a framework explaining how TF dysfunction simultaneously drives uncontrolled proliferation, impaired differentiation, and genomic instability. Here, TF is linked to cancer.