Mechanisms of CDK4/6 Inhibitor Resistance in Luminal Breast Cancer

被引：62

作者：

Li, Zhen ^{[1
]}

Zou, Wei ^{[2
]}

Zhang, Ji ^{[1
]}

Zhang, Yunjiao ^{[3
]}

Xu, Qi ^{[4
]}

Li, Siyuan ^{[5
]}

Chen, Ceshi ^{[5
,6
,7
,8
]}

机构：

[1] Kunming Med Univ, Affiliated Hosp 3, Dept Breast Surg 3, Kunming, Yunnan, Peoples R China

[2] Nanchang Univ, Queen Mary Inst, Nanchang, Jiangxi, Peoples R China

[3] Kunming Med Univ, Haiyuan Coll, Kunming, Yunnan, Peoples R China

[4] Univ Texas Austin, Inst Cellular & Mol Biol, Dept Mol Biosci, Austin, TX 78712 USA

[5] Chinese Acad Sci, Chinese Acad Sci & Yunnan Prov, Kunming Inst Zool, Key Lab Anim Models & Human Dis Mech, Kunming, Yunnan, Peoples R China

[6] Chinese Acad Sci, Kunming Inst Zool, KIZ CUHK Joint Lab Bioresources & Mol Res Common, Kunming, Yunnan, Peoples R China

[7] Shenzhen Univ, Shenzhen Peoples Hosp 2, Affiliated Hosp 1, Inst Translat Med, Shenzhen, Peoples R China

[8] Guangzhou Med Univ, Affiliated Canc Hosp & Inst, Guangzhou, Peoples R China

来源：

FRONTIERS IN PHARMACOLOGY | 2020年 / 11卷

基金：

国家重点研发计划;

关键词：

luminal breast cancer; endocrine resistance; upstream response signaling; downstream bypass signaling; CDK4; 6; inhibitor; CYCLIN-DEPENDENT KINASES; ENDOCRINE THERAPY RESISTANCE; PHASE-II; PREDICTIVE BIOMARKER; CDK6; INHIBITOR; TUMOR-GROWTH; ABEMACICLIB; PALBOCICLIB; FULVESTRANT; COMBINATION;

D O I：

10.3389/fphar.2020.580251

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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.

引用

页数：10

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