CDK7, a transcriptional CDK exhibiting CDK activating kinase activity on CDK2 and CDK9, has recently been found to be involved in the resistance mechanisms to CDK4/6i in CDK4/6i-resistant ER+/HER2− breast cancer cell models with loss of Rb and exhibiting cyclin E1 overexpression [84]. The gene discussed is ESR1; the disease is breast cancer.