PMID- 22114931
OWN - NLM
STAT- MEDLINE
DCOM- 20120625
LR  - 20220331
IS  - 1465-542X (Electronic)
IS  - 1465-5411 (Print)
IS  - 1465-5411 (Linking)
VI  - 13
IP  - 6
DP  - 2011
TI  - Mutations in the phosphatidylinositol 3-kinase pathway: role in tumor progression 
      and therapeutic implications in breast cancer.
PG  - 224
LID - 10.1186/bcr3039 [doi]
AB  - Mutations in genes that constitute the phosphatidylinositol 3-kinase (PI3K) 
      pathway occur in >70% of breast cancers. Clinical and experimental evidence 
      suggest that PI3K pathway activation promotes resistance to some of the current 
      breast cancer therapies. PI3K is a major signaling hub downstream of human 
      epidermal growth factor receptor (HER)2 and other receptor tyrosine kinases. PI3K 
      activates AKT, serum/glucocorticoid regulated kinase (SGK), 
      phosphoinositide-dependent kinase 1 (PDK1), mammalian target of rapamycin (mTOR), 
      and several other molecules involved in cell cycle progression and survival. In 
      estrogen receptor (ER)+ breast cancer cells, PI3K activation promotes 
      estrogen-dependent and -independent ER transcriptional activity, which, in turn, 
      may contribute to anti-estrogen resistance. Activation of this pathway also 
      confers resistance to HER2-targeted therapies. In experimental models of 
      resistance to anti-estrogens and HER2 inhibitors, pharmacological inhibition of 
      PI3K/AKT/mTOR has been shown to overcome drug resistance. Early clinical data 
      suggest that combined inhibition of either HER2 or ER plus inhibition of the PI3K 
      pathway might be an effective strategy for treatment of respective HER2+ and ER+ 
      breast cancers resistant to standard therapies. Here, we review alterations in 
      the PI3K pathway in breast cancer, their association with therapeutic resistance, 
      and the state of clinical development of PI3K pathway inhibitors.
FAU - Miller, Todd W
AU  - Miller TW
AD  - Department of Cancer Biology, Vanderbilt-Ingram Cancer Center, Vanderbilt 
      University, Nashville, TN 37232, USA.
FAU - Rexer, Brent N
AU  - Rexer BN
FAU - Garrett, Joan T
AU  - Garrett JT
FAU - Arteaga, Carlos L
AU  - Arteaga CL
LA  - eng
GR  - R01 CA080195/CA/NCI NIH HHS/United States
GR  - K08 CA143153/CA/NCI NIH HHS/United States
GR  - K99 CA142899/CA/NCI NIH HHS/United States
GR  - K99CA142899/CA/NCI NIH HHS/United States
GR  - P50 CA098131/CA/NCI NIH HHS/United States
GR  - R01 CA140594/CA/NCI NIH HHS/United States
GR  - P30 CA068485/CA/NCI NIH HHS/United States
GR  - K08CA143153/CA/NCI NIH HHS/United States
GR  - P50CA98131/CA/NCI NIH HHS/United States
GR  - P30CA68485/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20111101
PL  - England
TA  - Breast Cancer Res
JT  - Breast cancer research : BCR
JID - 100927353
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Receptors, Estrogen)
RN  - 0 (Receptors, Progesterone)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*therapeutic use
MH  - Breast Neoplasms/*drug therapy/*genetics
MH  - Disease Progression
MH  - Enzyme Inhibitors/*therapeutic use
MH  - Female
MH  - Humans
MH  - *Mutation
MH  - Phosphatidylinositol 3-Kinases/*genetics
MH  - Receptor, ErbB-2/genetics
MH  - Receptors, Estrogen/genetics
MH  - Receptors, Progesterone/genetics
MH  - Signal Transduction/drug effects/*genetics
PMC - PMC3315683
EDAT- 2011/11/26 06:00
MHDA- 2012/06/26 06:00
PMCR- 2012/05/01
CRDT- 2011/11/26 06:00
PHST- 2011/11/26 06:00 [entrez]
PHST- 2011/11/26 06:00 [pubmed]
PHST- 2012/06/26 06:00 [medline]
PHST- 2012/05/01 00:00 [pmc-release]
AID - bcr3039 [pii]
AID - 10.1186/bcr3039 [doi]
PST - ppublish
SO  - Breast Cancer Res. 2011;13(6):224. doi: 10.1186/bcr3039. Epub 2011 Nov 1.