However, despite this success, especially in endocrine-naive disease, resistance to CDK4/6 inhibitors eventually develops, and a significant proportion of patients with HR+/HER2− breast cancer fail to respond to CDK4/6 inhibitors in the second-line setting (>30%) or beyond (>60%) following progression on endocrine therapy [11, 13, 33]. The gene discussed is CDK4; the disease is breast cancer.