PMID- 22145099
OWN - NLM
STAT- MEDLINE
DCOM- 20121121
LR  - 20220410
IS  - 2159-8290 (Electronic)
IS  - 2159-8274 (Print)
IS  - 2159-8274 (Linking)
VI  - 1
IP  - 4
DP  - 2011 Sep
TI  - BIM expression in treatment-naive cancers predicts responsiveness to kinase 
      inhibitors.
PG  - 352-65
LID - 10.1158/2159-8290.CD-11-0106 [doi]
AB  - Cancers with specific genetic mutations are susceptible to selective kinase 
      inhibitors. However, there is a wide spectrum of benefit among cancers harboring 
      the same sensitizing genetic mutations. Herein, we measured apoptotic rates among 
      cell lines sharing the same driver oncogene following treatment with the 
      corresponding kinase inhibitor. There was a wide range of kinase 
      inhibitor-induced apoptosis despite comparable inhibition of the target and 
      associated downstream signaling pathways. Surprisingly, pretreatment RNA levels 
      of the BH3-only pro-apoptotic BIM strongly predicted the capacity of EGFR, HER2, 
      and PI3K inhibitors to induce apoptosis in EGFR-mutant, HER2-amplified, and 
      PIK3CA-mutant cancers, respectively, but BIM levels did not predict 
      responsiveness to standard chemotherapies. Furthermore, BIM RNA levels in 
      EGFR-mutant lung cancer specimens predicted response and duration of clinical 
      benefit from EGFR inhibitors. These findings suggest assessment of BIM levels in 
      treatment-naive tumor biopsies may indicate the degree of benefit from 
      single-agent kinase inhibitors in multiple oncogene-addiction paradigms.
CI  - (c)2011 AACR.
FAU - Faber, Anthony C
AU  - Faber AC
AD  - Massachusetts General Hospital Cancer Center, and Department of Medicine, Harvard 
      Medical School, Boston, Massachusetts 02129, USA.
FAU - Corcoran, Ryan B
AU  - Corcoran RB
FAU - Ebi, Hiromichi
AU  - Ebi H
FAU - Sequist, Lecia V
AU  - Sequist LV
FAU - Waltman, Belinda A
AU  - Waltman BA
FAU - Chung, Euiheon
AU  - Chung E
FAU - Incio, Joao
AU  - Incio J
FAU - Digumarthy, Subba R
AU  - Digumarthy SR
FAU - Pollack, Sarah F
AU  - Pollack SF
FAU - Song, Youngchul
AU  - Song Y
FAU - Muzikansky, Alona
AU  - Muzikansky A
FAU - Lifshits, Eugene
AU  - Lifshits E
FAU - Roberge, Sylvie
AU  - Roberge S
FAU - Coffman, Erik J
AU  - Coffman EJ
FAU - Benes, Cyril H
AU  - Benes CH
FAU - Gomez, Henry L
AU  - Gomez HL
FAU - Baselga, Jose
AU  - Baselga J
FAU - Arteaga, Carlos L
AU  - Arteaga CL
FAU - Rivera, Miguel N
AU  - Rivera MN
FAU - Dias-Santagata, Dora
AU  - Dias-Santagata D
FAU - Jain, Rakesh K
AU  - Jain RK
FAU - Engelman, Jeffrey A
AU  - Engelman JA
LA  - eng
GR  - R01 CA080195/CA/NCI NIH HHS/United States
GR  - P50CA090578/CA/NCI NIH HHS/United States
GR  - R01 CA137008/CA/NCI NIH HHS/United States
GR  - R01 CA137008-01/CA/NCI NIH HHS/United States
GR  - P50 CA098131/CA/NCI NIH HHS/United States
GR  - K08 CA120060/CA/NCI NIH HHS/United States
GR  - P50 CA090578/CA/NCI NIH HHS/United States
GR  - R01CA137008-01/CA/NCI NIH HHS/United States
GR  - K08 CA120060-01/CA/NCI NIH HHS/United States
GR  - R01 CA135257-01/CA/NCI NIH HHS/United States
GR  - R01 CA140594-02/CA/NCI NIH HHS/United States
GR  - P50 CA127003/CA/NCI NIH HHS/United States
GR  - R01CA140594/CA/NCI NIH HHS/United States
GR  - R01CA135257-01/CA/NCI NIH HHS/United States
GR  - P20 CA090578/CA/NCI NIH HHS/United States
GR  - R01 CA140594/CA/NCI NIH HHS/United States
GR  - P20 CA090578-02/CA/NCI NIH HHS/United States
GR  - P01 CA080124/CA/NCI NIH HHS/United States
GR  - R01 CA135257/CA/NCI NIH HHS/United States
GR  - P50 CA127003-03/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110722
PL  - United States
TA  - Cancer Discov
JT  - Cancer discovery
JID - 101561693
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (BCL2L11 protein, human)
RN  - 0 (BH3 Interacting Domain Death Agonist Protein)
RN  - 0 (BID protein, human)
RN  - 0 (Bcl-2-Like Protein 11)
RN  - 0 (Bcl2l11 protein, mouse)
RN  - 0 (Membrane Proteins)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Proto-Oncogene Proteins)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
CIN - Cancer Discov. 2011 Sep;1(4):289-90. doi: 10.1158/2159-8290.CD-11-0193. PMID: 
      22586609
MH  - Animals
MH  - Apoptosis/drug effects/genetics
MH  - Apoptosis Regulatory Proteins/*biosynthesis/*genetics/metabolism
MH  - BH3 Interacting Domain Death Agonist Protein/genetics/metabolism
MH  - Bcl-2-Like Protein 11
MH  - Cell Line, Tumor
MH  - Cohort Studies
MH  - ErbB Receptors/antagonists & inhibitors/genetics/metabolism
MH  - Female
MH  - Humans
MH  - Lung Neoplasms/*drug therapy/*genetics/metabolism
MH  - Membrane Proteins/*biosynthesis/*genetics/metabolism
MH  - Mice
MH  - Mice, Nude
MH  - Oncogenes
MH  - Phosphatidylinositol 3-Kinases/genetics/metabolism
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Protein Kinase Inhibitors/*pharmacology
MH  - Proto-Oncogene Proteins/*biosynthesis/*genetics/metabolism
MH  - Receptor, ErbB-2/antagonists & inhibitors/genetics/metabolism
MH  - Retrospective Studies
MH  - Signal Transduction/drug effects
PMC - PMC3229203
MID - NIHMS323250
OTO - NOTNLM
OT  - BIM
OT  - EGFR
OT  - HER2
OT  - apoptosis
OT  - oncogene addiction
EDAT- 2011/12/07 06:00
MHDA- 2012/12/10 06:00
PMCR- 2012/09/01
CRDT- 2011/12/07 06:00
PHST- 2011/12/07 06:00 [entrez]
PHST- 2011/12/07 06:00 [pubmed]
PHST- 2012/12/10 06:00 [medline]
PHST- 2012/09/01 00:00 [pmc-release]
AID - 2159-8290.CD-11-0106 [pii]
AID - 10.1158/2159-8290.CD-11-0106 [doi]
PST - ppublish
SO  - Cancer Discov. 2011 Sep;1(4):352-65. doi: 10.1158/2159-8290.CD-11-0106. Epub 2011 
      Jul 22.