RB1 and cancer: EGFR initiates a signaling cascade that leads to DNA synthesis and cell proliferation; and EGFR and PI3K initiate malignant transformation of cancer cells by activating other pathways such as Myc and Rb-E2F, which in turn leads to the formation of cyclinD/Cdk4 and cyclinE/Cdk2 complexes (Read et al., 2009).