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. 2017 Dec 11;32(6):761-776.e6.
doi: 10.1016/j.ccell.2017.11.006.

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

Xueqian Gong  1 , Lacey M Litchfield  1 , Yue Webster  1 , Li-Chun Chio  1 , Swee Seong Wong  1 , Trent R Stewart  1 , Michele Dowless  1 , Jack Dempsey  1 , Yi Zeng  1 , Raquel Torres  2 , Karsten Boehnke  2 , Cecilia Mur  2 , Carlos Marugán  2 , Carmen Baquero  2 , Chunping Yu  3 , Steven M Bray  1 , Isabella H Wulur  1 , Chen Bi  1 , Shaoyou Chu  1 , Hui-Rong Qian  1 , Philip W Iversen  1 , Farhana F Merzoug  1 , Xiang S Ye  3 , Christoph Reinhard  1 , Alfonso De Dios  1 , Jian Du  1 , Charles W Caldwell  1 , María José Lallena  2 , Richard P Beckmann  1 , Sean G Buchanan  4
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Free article

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

Xueqian Gong et al. Cancer Cell. .
Free article

Abstract

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.

Keywords: CCND1; CCND2; CCND3; CDK2; CDKN2A.

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