| Literature DB >> 29232554 |
Xueqian Gong1, Lacey M Litchfield1, Yue Webster1, Li-Chun Chio1, Swee Seong Wong1, Trent R Stewart1, Michele Dowless1, Jack Dempsey1, Yi Zeng1, Raquel Torres2, Karsten Boehnke2, Cecilia Mur2, Carlos Marugán2, Carmen Baquero2, Chunping Yu3, Steven M Bray1, Isabella H Wulur1, Chen Bi1, Shaoyou Chu1, Hui-Rong Qian1, Philip W Iversen1, Farhana F Merzoug1, Xiang S Ye3, Christoph Reinhard1, Alfonso De Dios1, Jian Du1, Charles W Caldwell1, María José Lallena2, Richard P Beckmann1, Sean G Buchanan4.
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.Entities:
Keywords: CCND1; CCND2; CCND3; CDK2; CDKN2A
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Year: 2017 PMID： 29232554 DOI： 10.1016/j.ccell.2017.11.006
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743