PMID- 14734498
OWN - NLM
STAT- MEDLINE
DCOM- 20040224
LR  - 20191108
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 10
IP  - 1 Pt 2
DP  - 2004 Jan 1
TI  - Regulatory nodes that integrate and coordinate signaling as potential targets for 
      breast cancer therapy.
PG  - 396S-401S
AB  - Blockade of the estrogen receptor (ER) with antiestrogens and aromatase 
      inhibitors is effective in the treatment of breast cancer. Why ER plays such a 
      dominant role in breast cancer and represents such an excellent target remains to 
      be defined. The ability of ER to respond to multiple inputs and to control 
      expression of multiple downstream genes may be one of the reasons why ER is such 
      a powerful target for breast cancer treatment. The recent modest performance of a 
      number of targeted therapies in breast cancer has raised the question whether we 
      will ever develop therapies that have such success as antiestrogens. Targeted 
      therapies tend to inhibit a single pathway that is probably altered in only a 
      subset of patients. Even within this subset, only a limited number of patients 
      respond. The evidence that virtually all pathways can cross-talk and that they 
      exhibit several layers of redundancy reveals a complexity of signaling networks 
      that may defy the generation of targeted therapies with efficacy similar to 
      antiestrogens. However, there are clearly regulatory nodes that can integrate 
      multiple upstream inputs and elicit diverse downstream outputs. We provide 
      evidence and rationales for integrins, insulin receptor substrates (IRSs), and 
      cyclin D1 as potential therapeutic targets. These proteins, similar to ER, can 
      integrate and coordinate multiple signals in breast cancer cells and thus mediate 
      diverse aspects of breast cancer progression. New treatment targets will emerge 
      in light of more global models of signal transduction that fully integrate all 
      aspects of cell biology such as the role of the extracellular matrix and will 
      hopefully result in the development of targeted therapies that show efficacy 
      similar to antiestrogens.
FAU - Cui, Xiaojiang
AU  - Cui X
AD  - Breast Center, Baylor College of Medicine, Houston, Texas, USA.
FAU - Lee, Adrian V
AU  - Lee AV
LA  - eng
GR  - R01CA94118/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Estrogens)
RN  - 0 (Growth Substances)
RN  - 0 (Receptors, Estrogen)
RN  - 136601-57-5 (Cyclin D1)
SB  - IM
MH  - Breast Neoplasms/*therapy
MH  - Cell Nucleus/metabolism
MH  - Cyclin D1/metabolism
MH  - Cytoplasm/metabolism
MH  - Disease Progression
MH  - Estrogens/metabolism
MH  - Extracellular Matrix/metabolism
MH  - Gene Expression Regulation, Neoplastic
MH  - Growth Substances/metabolism
MH  - Humans
MH  - Neoplasms, Hormone-Dependent/metabolism
MH  - Receptors, Estrogen/metabolism
MH  - *Signal Transduction
EDAT- 2004/01/22 05:00
MHDA- 2004/02/26 05:00
CRDT- 2004/01/22 05:00
PHST- 2004/01/22 05:00 [pubmed]
PHST- 2004/02/26 05:00 [medline]
PHST- 2004/01/22 05:00 [entrez]
AID - 10.1158/1078-0432.ccr-031205 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2004 Jan 1;10(1 Pt 2):396S-401S. doi: 
      10.1158/1078-0432.ccr-031205.