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

Autor:	Gong X; Eli Lilly and Company, Indianapolis, IN 46285, USA., Litchfield LM; Eli Lilly and Company, Indianapolis, IN 46285, USA., Webster Y; Eli Lilly and Company, Indianapolis, IN 46285, USA., Chio LC; Eli Lilly and Company, Indianapolis, IN 46285, USA., Wong SS; Eli Lilly and Company, Indianapolis, IN 46285, USA., Stewart TR; Eli Lilly and Company, Indianapolis, IN 46285, USA., Dowless M; Eli Lilly and Company, Indianapolis, IN 46285, USA., Dempsey J; Eli Lilly and Company, Indianapolis, IN 46285, USA., Zeng Y; Eli Lilly and Company, Indianapolis, IN 46285, USA., Torres R; Eli Lilly and Company, Alcobendas, Madrid, Spain., Boehnke K; Eli Lilly and Company, Alcobendas, Madrid, Spain., Mur C; Eli Lilly and Company, Alcobendas, Madrid, Spain., Marugán C; Eli Lilly and Company, Alcobendas, Madrid, Spain., Baquero C; Eli Lilly and Company, Alcobendas, Madrid, Spain., Yu C; Eli Lilly and Company, Shanghai, China., Bray SM; Eli Lilly and Company, Indianapolis, IN 46285, USA., Wulur IH; Eli Lilly and Company, Indianapolis, IN 46285, USA., Bi C; Eli Lilly and Company, Indianapolis, IN 46285, USA., Chu S; Eli Lilly and Company, Indianapolis, IN 46285, USA., Qian HR; Eli Lilly and Company, Indianapolis, IN 46285, USA., Iversen PW; Eli Lilly and Company, Indianapolis, IN 46285, USA., Merzoug FF; Eli Lilly and Company, Indianapolis, IN 46285, USA., Ye XS; Eli Lilly and Company, Shanghai, China., Reinhard C; Eli Lilly and Company, Indianapolis, IN 46285, USA., De Dios A; Eli Lilly and Company, Indianapolis, IN 46285, USA., Du J; Eli Lilly and Company, Indianapolis, IN 46285, USA., Caldwell CW; Eli Lilly and Company, Indianapolis, IN 46285, USA., Lallena MJ; Eli Lilly and Company, Alcobendas, Madrid, Spain., Beckmann RP; Eli Lilly and Company, Indianapolis, IN 46285, USA., Buchanan SG; Eli Lilly and Company, Indianapolis, IN 46285, USA. Electronic address: buchananse@lilly.com.
Jazyk:	angličtina
Zdroj:	Cancer cell [Cancer Cell] 2017 Dec 11; Vol. 32 (6), pp. 761-776.e6.
DOI:	10.1016/j.ccell.2017.11.006
Abstrakt:	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. (Copyright © 2017 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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