Linked Life Data

15163844

Source:http://linkedlifedata.com/resource/pubmed/id/15163844

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2004-5-27
pubmed:abstractText
Endocrine therapy is the most effective systemic treatment for patients with hormone-receptor-positive (HR(+)) breast cancer. Unfortunately, efficacy is often limited by the onset of resistance, which is almost inevitable for patients with advanced disease. Several patterns of endocrine resistance are recognizable clinically, including: A) tumors that are inherently insensitive to all attempts at estrogen receptor (ER) targeting despite expression of ER (pan-endocrine therapy resistance); B) tumors that are estrogen dependent but resistant to one or more specific endocrine therapies (agent-selective resistance); and C) tumors that initially respond but subsequently progress (acquired resistance). Current insights into the molecular basis for these resistance patterns are rudimentary, but are most clearly illuminated by investigations that focus on the crosstalk between the ErbB or HER peptide growth factor family and the ER. The data are sufficiently compelling to be addressed by ongoing clinical trials that examine combinations of endocrine agents and either trastuzumab (Herceptin; Genentech, Inc.; South San Francisco, CA) or ErbB-specific tyrosine kinase (TK) inhibitors. Preliminary data from a small "proof of concept" phase II study of letrozole (Femara; Novartis Pharmaceuticals Corporation; East Hanover, NJ) and trastuzumab demonstrated durable responses despite tamoxifen (Nolvadex; AstraZeneca Pharmaceuticals; Wilmington, DE) resistance. Efficacy was variable, however, despite the selection of patients on the basis of ER and ErbB-2 coexpression. Complicating matters further, resistance often occurs in the absence of any evidence for ErbB TK family member expression. In the absence of a clear target, common downstream signal transduction proteins that are known to intersect with the ER pathway can be inhibited to address resistance, including G proteins with farnesyltransferase inhibitors and molecular target of rapamycin (mTOR) with rapamycin analogues. With a number of phase III clinical trials now under way, major advances in the endocrine treatment of advanced disease are possible.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Alkyl and Aryl Transferases, http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, http://linkedlifedata.com/resource/pubmed/chemical/Aromatase Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Farnesyltranstransferase, http://linkedlifedata.com/resource/pubmed/chemical/Immunosuppressive Agents, http://linkedlifedata.com/resource/pubmed/chemical/Nitriles, http://linkedlifedata.com/resource/pubmed/chemical/Receptor, erbB-2, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Estrogen, http://linkedlifedata.com/resource/pubmed/chemical/Sirolimus, http://linkedlifedata.com/resource/pubmed/chemical/Tamoxifen, http://linkedlifedata.com/resource/pubmed/chemical/Triazoles, http://linkedlifedata.com/resource/pubmed/chemical/letrozole, http://linkedlifedata.com/resource/pubmed/chemical/temsirolimus
pubmed:status
MEDLINE
pubmed:issn
1083-7159
pubmed:author
pubmed:issnType
Print
pubmed:volume
9 Suppl 3
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
20-6
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Overcoming endocrine therapy resistance by signal transduction inhibition.
pubmed:affiliation
Siteman Cancer Center, Washington University, St. Louis, Missouri 63110, USA. mellis@wustl.edu
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't