RB1 and cancer: Dysregulation of this canonical RB function is central in cancer, with components of the CDK4/6-RB pathway often displaying mutations that will result in sustained cell proliferation; for instance, in tumors that retain RB expression, uncontrolled cell cycle activity may be due to the amplification of the cyclin D1 gene (CCND1) and CDK4, activating CDK4/6 mutations or silencing of CDK inhibitors (CKI) [67,68].