PMID- 29232554
OWN - NLM
STAT- MEDLINE
DCOM- 20171220
LR  - 20191210
IS  - 1878-3686 (Electronic)
IS  - 1535-6108 (Linking)
VI  - 32
IP  - 6
DP  - 2017 Dec 11
TI  - Genomic Aberrations that Activate D-type Cyclins Are Associated with Enhanced 
      Sensitivity to the CDK4 and CDK6 Inhibitor Abemaciclib.
PG  - 761-776.e6
LID - S1535-6108(17)30509-3 [pii]
LID - 10.1016/j.ccell.2017.11.006 [doi]
AB  - 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.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Gong, Xueqian
AU  - Gong X
AD  - Eli Lilly and Company, Indianapolis, IN 46285, USA.
FAU - Litchfield, Lacey M
AU  - Litchfield LM
AD  - Eli Lilly and Company, Indianapolis, IN 46285, USA.
FAU - Webster, Yue
AU  - Webster Y
AD  - Eli Lilly and Company, Indianapolis, IN 46285, USA.
FAU - Chio, Li-Chun
AU  - Chio LC
AD  - Eli Lilly and Company, Indianapolis, IN 46285, USA.
FAU - Wong, Swee Seong
AU  - Wong SS
AD  - Eli Lilly and Company, Indianapolis, IN 46285, USA.
FAU - Stewart, Trent R
AU  - Stewart TR
AD  - Eli Lilly and Company, Indianapolis, IN 46285, USA.
FAU - Dowless, Michele
AU  - Dowless M
AD  - Eli Lilly and Company, Indianapolis, IN 46285, USA.
FAU - Dempsey, Jack
AU  - Dempsey J
AD  - Eli Lilly and Company, Indianapolis, IN 46285, USA.
FAU - Zeng, Yi
AU  - Zeng Y
AD  - Eli Lilly and Company, Indianapolis, IN 46285, USA.
FAU - Torres, Raquel
AU  - Torres R
AD  - Eli Lilly and Company, Alcobendas, Madrid, Spain.
FAU - Boehnke, Karsten
AU  - Boehnke K
AD  - Eli Lilly and Company, Alcobendas, Madrid, Spain.
FAU - Mur, Cecilia
AU  - Mur C
AD  - Eli Lilly and Company, Alcobendas, Madrid, Spain.
FAU - Marugan, Carlos
AU  - Marugan C
AD  - Eli Lilly and Company, Alcobendas, Madrid, Spain.
FAU - Baquero, Carmen
AU  - Baquero C
AD  - Eli Lilly and Company, Alcobendas, Madrid, Spain.
FAU - Yu, Chunping
AU  - Yu C
AD  - Eli Lilly and Company, Shanghai, China.
FAU - Bray, Steven M
AU  - Bray SM
AD  - Eli Lilly and Company, Indianapolis, IN 46285, USA.
FAU - Wulur, Isabella H
AU  - Wulur IH
AD  - Eli Lilly and Company, Indianapolis, IN 46285, USA.
FAU - Bi, Chen
AU  - Bi C
AD  - Eli Lilly and Company, Indianapolis, IN 46285, USA.
FAU - Chu, Shaoyou
AU  - Chu S
AD  - Eli Lilly and Company, Indianapolis, IN 46285, USA.
FAU - Qian, Hui-Rong
AU  - Qian HR
AD  - Eli Lilly and Company, Indianapolis, IN 46285, USA.
FAU - Iversen, Philip W
AU  - Iversen PW
AD  - Eli Lilly and Company, Indianapolis, IN 46285, USA.
FAU - Merzoug, Farhana F
AU  - Merzoug FF
AD  - Eli Lilly and Company, Indianapolis, IN 46285, USA.
FAU - Ye, Xiang S
AU  - Ye XS
AD  - Eli Lilly and Company, Shanghai, China.
FAU - Reinhard, Christoph
AU  - Reinhard C
AD  - Eli Lilly and Company, Indianapolis, IN 46285, USA.
FAU - De Dios, Alfonso
AU  - De Dios A
AD  - Eli Lilly and Company, Indianapolis, IN 46285, USA.
FAU - Du, Jian
AU  - Du J
AD  - Eli Lilly and Company, Indianapolis, IN 46285, USA.
FAU - Caldwell, Charles W
AU  - Caldwell CW
AD  - Eli Lilly and Company, Indianapolis, IN 46285, USA.
FAU - Lallena, Maria Jose
AU  - Lallena MJ
AD  - Eli Lilly and Company, Alcobendas, Madrid, Spain.
FAU - Beckmann, Richard P
AU  - Beckmann RP
AD  - Eli Lilly and Company, Indianapolis, IN 46285, USA.
FAU - Buchanan, Sean G
AU  - Buchanan SG
AD  - Eli Lilly and Company, Indianapolis, IN 46285, USA. Electronic address: 
      buchananse@lilly.com.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Cancer Cell
JT  - Cancer cell
JID - 101130617
RN  - 0 (Aminopyridines)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Benzimidazoles)
RN  - 0 (Cyclin D)
RN  - 60UAB198HK (abemaciclib)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 4)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 6)
SB  - IM
CIN - Cancer Cell. 2017 Dec 11;32(6):721-723. PMID: 29232548
MH  - Aminopyridines/*pharmacology
MH  - Animals
MH  - Antineoplastic Agents/pharmacology
MH  - Benzimidazoles/*pharmacology
MH  - Cell Proliferation/drug effects
MH  - Clinical Trials, Phase I as Topic
MH  - Cyclin D/genetics/*metabolism
MH  - Cyclin-Dependent Kinase 4/antagonists & inhibitors
MH  - Cyclin-Dependent Kinase 6/antagonists & inhibitors
MH  - Female
MH  - Humans
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Neoplasms/drug therapy/*genetics/metabolism
MH  - Xenograft Model Antitumor Assays
OTO - NOTNLM
OT  - CCND1
OT  - CCND2
OT  - CCND3
OT  - CDK2
OT  - CDKN2A
EDAT- 2017/12/13 06:00
MHDA- 2017/12/21 06:00
CRDT- 2017/12/13 06:00
PHST- 2017/02/20 00:00 [received]
PHST- 2017/08/10 00:00 [revised]
PHST- 2017/11/08 00:00 [accepted]
PHST- 2017/12/13 06:00 [entrez]
PHST- 2017/12/13 06:00 [pubmed]
PHST- 2017/12/21 06:00 [medline]
AID - S1535-6108(17)30509-3 [pii]
AID - 10.1016/j.ccell.2017.11.006 [doi]
PST - ppublish
SO  - Cancer Cell. 2017 Dec 11;32(6):761-776.e6. doi: 10.1016/j.ccell.2017.11.006.