Linked Life Data

12959183

Source:http://linkedlifedata.com/resource/pubmed/id/12959183

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2003-9-8
pubmed:abstractText
Characterization of intracellular signaling pathways should lead to a better understanding of ovarian epithelial carcinogenesis and provide an opportunity to interfere with signal transduction targets involved in ovarian tumor cell growth, survival, and progression. Challenges toward such an effort are significant because many of these signals are part of cascades within an intricate and likely redundant intracellular signaling network (Fig.1). For instance, a given signal may activate a dual intracellular pathway (ie, MEK1-MAPK and PI3K/Akt required for fibronectin-dependent activation of matrix metalloproteinase 9). A single pathway also may transduce more than one biologic or oncogenic signal (ie, PI3K signaling in epithelial and endothelial cell growth and sprouting of neovessels). Despite these challenges, evidence for therapeutic targeting of signal transduction pathways is accumulating in human cancer. For instance, the EGF-specific tyrosine kinase inhibitor ZD 1839 (Iressa) may have a beneficial therapeutic effect on ovarian epithelial cancer. Therapy of this cancer may include inhibitors of PI kinase (quercetin), ezrin and PIP kinase (genistein). The G protein-coupled family of receptors, including LPA, also is an attractive target to drugs, although their frequent pleiotropic functions may be at times toxic and lack specificity. Because of the lack of notable toxicity, PI3K/Akt pathway inhibitors such as FTIs are a promising targeted therapy of ovarian epithelial cancer. Increasing insight into the oncogenic pathways involved in ovarian epithelial cancer also is helping clinicians to understand better the phenomenon of chemoresistance in this malignancy. Oncogenic activation of gamma-synuclein promotes cell survival and provides resistance to paclitaxel, but such a resistance is partially overcome by an MEK inhibitor that suppresses ERK activity. Ovarian epithelial cancer is a complex group of neoplasms with an overall poor prognosis. Comprehension of this cancer pathobiology suffers because of an incomplete understanding of precursor lesions and the absence of an orthotopic animal model until very recently. It can be predicted with confidence, however, that the discovery of potent inhibitors of signal transduction and the development of discovery tools, such as proteomics and metabolomics, may change the way by which clinicians may now address basic biomedical questions in this insidious and lethal disease.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0889-8588
pubmed:author
pubmed:issnType
Print
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
927-43
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Oncogenic pathways implicated in ovarian epithelial cancer.
pubmed:affiliation
Department of Pathology and Laboratory Medicine, University of South Florida College of Medicine, 12901 Bruce B. Downs Boulevard, MDC Box 11, Tampa, FL 33612, USA. snicosia@hsc.usf.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Review