RB1 and cancer: For example, the proto-oncogenes K-RAS and BRAF, the mitogen-activated protein kinase (MAPK), the extra-cellular signal-regulated kinase (ERK), the phosphoinositide 3-kinase (PI3K)-PTEN-AKT, and CDK4/6-Rb signaling play essential roles in cancer initiation, promotion, and progression [10,11,12].