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

  
@article{APS10262,
	author = {Xia-qing Xu and Xiao-hui Pan and Ting-ting Wang and Jian Wang and Bo Yang and Qiao-jun He and Ling Ding},
	title = {Intrinsic and acquired resistance to CDK4/6 inhibitors and potential overcoming strategies},
	journal = {Acta Pharmacologica Sinica},
	volume = {42},
	number = {2},
	year = {2021},
	keywords = {},
	abstract = {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.},
	url = {http://www.chinaphar.com/article/view/10262}
}