Targeting Cell Cycle in Breast Cancer: CDK4/6 Inhibitors

被引：91

作者：

Piezzo, Michela ^{[1
]}

Cocco, Stefania ^{[1
]}

Caputo, Roberta ^{[1
]}

Cianniello, Daniela ^{[1
]}

Di Gioia, Germira ^{[1
]}

Di Lauro, Vincenzo ^{[1
]}

Fusco, Giuseppina ^{[1
]}

Martinelli, Claudia ^{[2
]}

Nuzzo, Francesco ^{[1
]}

Pensabene, Matilde ^{[1
]}

De Laurentiis, Michelino ^{[1
]}

机构：

[1] Ist Nazl Tumori IRCCS Fdn G Pascale, Dept Breast & Thorac Oncol, Div Breast Med Oncol, I-80131 Naples, Italy

[2] Univ Naples Federico II, Dept Clin Med & Surg, I-80131 Naples, Italy

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2020年 / 21卷 / 18期

关键词：

cell cycle; cyclin-dependent kinase; cancer; metastatic breast cancer; hormone therapy; CDK4; 6; inhibitors; hormone receptors; therapies; DEPENDENT KINASE 4/6; ANTITUMOR-ACTIVITY; OPEN-LABEL; ENDOCRINE RESISTANCE; 1ST-LINE TREATMENT; PLUS PALBOCICLIB; PHASE-II; COMBINATION; FULVESTRANT; ABEMACICLIB;

D O I：

10.3390/ijms21186479

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Deregulation of cell cycle, via cyclin D/CDK/pRb pathway, is frequently observed in breast cancer lending support to the development of drugs targeting the cell cycle control machinery, like the inhibitors of the cycline-dependent kinases (CDK) 4 and 6. Up to now, three CDK4/6 inhibitors have been approved by FDA for the treatment of hormone receptor-positive (HR+), HER2-negative metastatic breast cancer. These agents have been effective in improving the clinical outcomes, but the development of intrinsic or acquired resistance can limit the efficacy of these treatments. Clinical and translational research is now focused on investigation of the mechanism of sensitivity/resistance to CDK4/6 inhibition and novel therapeutic strategies aimed to improve clinical outcomes. This review summarizes the available knowledge regarding CDK4/6 inhibitor, the discovery of new biomarkers of response, and the biological rationale for new combination strategies of treatment.

引用

页码：1 / 23

页数：23

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