The CDK4/6-RB pathway is abnormally activated in a variety of cancers, characterized by the abnormal amplification of genes related to the pathway and resistance to inhibition by cyclin-dependent kinase inhibitors (CKIs), including members of the INK4 family (p16INK4A, p15INK4B, p18INK4C, and p19INK4D) [43]. The gene discussed is CDKN2C; the disease is cancer.