Facing the CDK4/6i resistance dilemma in patients with breast cancer, exploration of the resistance mechanism and possible reverse strategy: A narrative review

Breast cancer is one of the highest rates of malignancy of women, approximate 70% metastatic breast cancer are hormone receptor positive (HR+) and human epidermal growth factor receptor 2 negative (HER2−). Hormone therapy is the primary strategy of HR+/HER2− metastatic breast cancer. With the permission of cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i), progress free survival and overall survival were significantly licensed. However, inevitable outcome of CDK4/6i resistance has become the main reason that restricts the clinical benefit of patients. In recent years, the research on dealing with drug resistance has become a hot topic, a large number of molecular mechanisms have been focused, and a lot of experiments have been carried out at the preclinical level. This review summarizes the current knowledge of CDK4/6i resistance mechanism, systematically expounds the signaling pathways and targets leading to CDK4/6i resistance, analyzes different ways and mechanisms, and provides theoretical guidance for the clinical reversal of endocrine therapy resistance.