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Genomic Aberrations that Activate D-type Cyclins Are Associated with Enhanced Sensitivity to the CDK4 and CDK6 Inhibitor Abemaciclib

Authors :
Swee Seong Wong
Michele Dowless
Alfonso De Dios
Chen Bi
Xueqian Gong
Richard P. Beckmann
Carlos Marugán
Yi Zeng
Xiang S. Ye
Li-Chun Chio
Lacey M. Litchfield
Farhana F. Merzoug
Jack A. Dempsey
Shaoyou Chu
Hui-Rong Qian
Christoph Reinhard
Karsten Boehnke
Trent R. Stewart
Yue Webster
Maria Jose Lallena
Cecilia Mur
Sean Buchanan
Isabella H. Wulur
Charles W. Caldwell
Steven M. Bray
Jian Du
Chunping Yu
Philip W. Iversen
Raquel Torres
Carmen Baquero
Source :
Cancer Cell. 32:761-776.e6
Publication Year :
2017
Publisher :
Elsevier BV, 2017.

Abstract

Summary Most cancers preserve functional retinoblastoma (Rb) and may, therefore, respond to inhibition of D-cyclin-dependent Rb kinases, CDK4 and CDK6. To date, CDK4/6 inhibitors have shown promising clinical activity in breast cancer and lymphomas, but it is not clear which additional Rb-positive cancers might benefit from these agents. No systematic survey to compare relative sensitivities across tumor types and define molecular determinants of response has been described. We report a subset of cancers highly sensitive to CDK4/6 inhibition and characterized by various genomic aberrations known to elevate D-cyclin levels and describe a recurrent CCND1 3′UTR mutation associated with increased expression in endometrial cancer. The results suggest multiple additional classes of cancer that may benefit from CDK4/6-inhibiting drugs such as abemaciclib.

Details

ISSN :
15356108
Volume :
32
Database :
OpenAIRE
Journal :
Cancer Cell
Accession number :
edsair.doi.dedup.....6bf0aa6fc912e9e26c4aed0ea43f0749
Full Text :
https://doi.org/10.1016/j.ccell.2017.11.006