Although the FDA approvals of the CDK4/6 inhibitors (CDK4/6i) palbociclib, ribociclib, and abemaciclib have transformed the treatment of metastatic hormone receptor-positive (HR+) and HER2-negative (HER2−) breast cancer, they remain a noncurative treatment option, as the development of resistance is common and nearly inevitable (3–5). The gene discussed is CDK4; the disease is breast cancer.