PMID- 23845444
OWN - NLM
STAT- MEDLINE
DCOM- 20130916
LR  - 20211203
IS  - 1878-3686 (Electronic)
IS  - 1535-6108 (Linking)
VI  - 24
IP  - 1
DP  - 2013 Jul 8
TI  - Targeting BCL-2 with the BH3 mimetic ABT-199 in estrogen receptor-positive breast 
      cancer.
PG  - 120-9
LID - S1535-6108(13)00278-X [pii]
LID - 10.1016/j.ccr.2013.06.002 [doi]
AB  - The prosurvival protein BCL-2 is frequently overexpressed in estrogen receptor 
      (ER)-positive breast cancer. We have generated ER-positive primary breast tumor 
      xenografts that recapitulate the primary tumors and demonstrate that the BH3 
      mimetic ABT-737 markedly improves tumor response to the antiestrogen tamoxifen. 
      Despite abundant BCL-XL expression, similar efficacy was observed with the BCL-2 
      selective inhibitor ABT-199, revealing that BCL-2 is a crucial target. 
      Unexpectedly, BH3 mimetics were found to counteract the side effect of 
      tamoxifen-induced endometrial hyperplasia. Moreover, BH3 mimetics synergized with 
      phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) 
      inhibitors in eliciting apoptosis. Importantly, these two classes of inhibitor 
      further enhanced tumor response in combination therapy with tamoxifen. 
      Collectively, our findings provide a rationale for the clinical evaluation of BH3 
      mimetics in therapy for breast cancer.
CI  - Copyright (c) 2013 Elsevier Inc. All rights reserved.
FAU - Vaillant, Francois
AU  - Vaillant F
AD  - ACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of 
      Medical Research, Parkville, VIC 3052, Australia.
FAU - Merino, Delphine
AU  - Merino D
FAU - Lee, Lily
AU  - Lee L
FAU - Breslin, Kelsey
AU  - Breslin K
FAU - Pal, Bhupinder
AU  - Pal B
FAU - Ritchie, Matthew E
AU  - Ritchie ME
FAU - Smyth, Gordon K
AU  - Smyth GK
FAU - Christie, Michael
AU  - Christie M
FAU - Phillipson, Louisa J
AU  - Phillipson LJ
FAU - Burns, Christopher J
AU  - Burns CJ
FAU - Mann, G Bruce
AU  - Mann GB
FAU - Visvader, Jane E
AU  - Visvader JE
FAU - Lindeman, Geoffrey J
AU  - Lindeman GJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Cell
JT  - Cancer cell
JID - 101130617
RN  - 0 (ABT-737)
RN  - 0 (Biphenyl Compounds)
RN  - 0 (Bridged Bicyclo Compounds, Heterocyclic)
RN  - 0 (Nitrophenols)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Piperazines)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Receptors, Estrogen)
RN  - 0 (Sulfonamides)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - N54AIC43PW (venetoclax)
SB  - IM
CIN - Breast Cancer Res. 2013;15(5):317. PMID: 24172207
MH  - Animals
MH  - Biphenyl Compounds/pharmacology
MH  - Breast Neoplasms/chemistry/*drug therapy/pathology
MH  - Bridged Bicyclo Compounds, Heterocyclic/*pharmacology
MH  - Female
MH  - Humans
MH  - Mice
MH  - Mice, SCID
MH  - Nitrophenols/pharmacology
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Piperazines/pharmacology
MH  - Proto-Oncogene Proteins c-bcl-2/*antagonists & inhibitors
MH  - Receptors, Estrogen/*analysis
MH  - Sulfonamides/*pharmacology
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors
MH  - Xenograft Model Antitumor Assays
EDAT- 2013/07/13 06:00
MHDA- 2013/09/17 06:00
CRDT- 2013/07/13 06:00
PHST- 2013/03/12 00:00 [received]
PHST- 2013/05/16 00:00 [revised]
PHST- 2013/06/03 00:00 [accepted]
PHST- 2013/07/13 06:00 [entrez]
PHST- 2013/07/13 06:00 [pubmed]
PHST- 2013/09/17 06:00 [medline]
AID - S1535-6108(13)00278-X [pii]
AID - 10.1016/j.ccr.2013.06.002 [doi]
PST - ppublish
SO  - Cancer Cell. 2013 Jul 8;24(1):120-9. doi: 10.1016/j.ccr.2013.06.002.