机构：[1]Department of the Third Breast Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, China,[2]Queen Mary Institute, Nanchang University, Nanchang, China,[3]Kunming Medical University Haiyuan College, Kunming, China,[4]Department of Molecular Biosciences, Institute of Cellular and Molecular Biology, The University of Texas, Austin, TX, United States,[5]Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China,[6]KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China,[7]Institute of Translation Medicine, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, China,深圳市第二人民医院深圳医学信息中心[8]Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China
As a new-generation CDK inhibitor, a CDK4/6 inhibitor combined with endocrine therapy has been successful in the treatment of advanced estrogen receptor-positive (ER+) breast cancer. Although there has been overall progress in the treatment of cancer, drug resistance is an emerging cause for breast cancer-related death. Overcoming CDK4/6 resistance is an urgent problem. Overactivation of the cyclin-CDK-Rb axis related to uncontrolled cell proliferation is the main cause of CDK4/6 inhibitor resistance; however, the underlying mechanisms need to be clarified further. We review various resistance mechanisms of CDK4/6 inhibitors in luminal breast cancer. The cell signaling pathways involved in therapy resistance are divided into two groups: upstream response mechanisms and downstream bypass mechanisms. Finally, we discuss possible strategies to overcome CDK4/6 inhibitor resistance and identify novel resistance targets for future clinical application.
基金：
This studywas supported in part by grants from the National Key R&D
Program of China [2018YFC2000400], the National Nature Science
Foundation of China [81830087, U1602221, 31771516], Science and
Technology Innovation Team of Yunnan Province [2018HC002,
2019HC005], Basic Research Program of Yunnan Province
[2019FE001(-309)], and Research Institutions attached to the Health
and Family Planning Commission of Yunnan Province [2017NS180].
第一作者机构：[1]Department of the Third Breast Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, China,
通讯作者：
通讯机构：[5]Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China,[6]KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China,[7]Institute of Translation Medicine, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, China,[8]Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China
推荐引用方式(GB/T 7714)：
Zhen Li,Wei Zou,Ji Zhang,et al.Mechanisms of CDK4/6 Inhibitor Resistance in Luminal Breast Cancer[J].FRONTIERS IN PHARMACOLOGY.2020,11:doi:10.3389/fphar.2020.580251.
APA：
Zhen Li,Wei Zou,Ji Zhang,Yunjiao Zhang,Qi Xu...&Ceshi Chen.(2020).Mechanisms of CDK4/6 Inhibitor Resistance in Luminal Breast Cancer.FRONTIERS IN PHARMACOLOGY,11,
MLA：
Zhen Li,et al."Mechanisms of CDK4/6 Inhibitor Resistance in Luminal Breast Cancer".FRONTIERS IN PHARMACOLOGY 11.(2020)
