Intrinsic and acquired resistance to CDK4/6 inhibitors and potential overcoming strategies

• 来源期刊: 中国药理学报（英文版）
• 年，卷（期）: 2021,（2）
• 所属期刊栏目: Review Article
• 页码范围: 171-178
• 页数: 8页
• 语种: 英文
• DOI: 10.1038/S41401-020-0416-4

摘要

Abnormal activation of the cyclin-dependent kinases(CDKs),which result in aberrant cell proliferation,is one of the inherent characteristics of tumor.Thus targeting the activity of CDKs represents a promising tumor therapeutic strategy.Currently,the specific inhibitors that target CDK4 and CDK6 have been approved for the treatment of estrogen receptor positive,human epidermal growth factor receptor 2 negative(ER+HER2-)breast cancer in combination with endocrine therapy;other combination strategies are being tested in a number of clinical trials.However,the acquired resistance to CDK4/6 inhibitors has emerged.As the cell cycle is orchestrated by a series of biological events,the alterations of other molecular events that regulate the cell cycle progression may be involved in intrinsic resistance to CDK4/6 inhibitors.In this review we mainly discuss the mechanisms underlying intrinsic resistance and acquired resistance to CDK4/6 inhibitors as well as combination strategies with other signal pathway inhibitors being tested in clinical and pre-clinical studies,to extend the use of CDK4/6 inhibitors in tumor treatment.