Linked Life Data

14528284

Source:http://linkedlifedata.com/resource/pubmed/id/14528284

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
42
pubmed:dateCreated
2003-10-6
pubmed:abstractText
Neoplastic transformation is often related to abnormal activation of growth factor receptors and their signaling pathways. The concept of targeting specific tumorigenic receptors and/or signaling molecules has been validated by the development and successful clinical application of drugs acting against the epidermal growth factor receptor 2 (HER2/neu, Erb2), the epidermal growth factor receptor 1 (EGFR, HER1), the Brc-Abl kinase, the platelet-derived growth factor receptor, and c-kit. This review will focus on the next promising therapeutic target, the insulin-like growth factor I receptor (IGF-IR). IGF-IR has been implicated in a number of neoplastic diseases, including several common carcinomas. From a pharmaceutical standpoint, of particular importance is that IGF-IR appears to be required for many transforming agents (genetic, viral, chemical) to act, but is not obligatory for the function of normal adult cells. The tumorigenic potential of IGF-IR is mediated through its antiapoptotic and transforming signaling, and in some cases through induction of prometastatic pathways. Preclinical studies demonstrated that downregulation of IGF-IR reversed the neoplastic phenotype and sensitized cells to antitumor treatments. The strategies to block IGF-IR function employed anti-IGF-IR antibodies, small-molecule inhibitors of the IGF-IR tyrosine kinase, antisense oligodeoxynucleotides and antisense RNA, small inhibitory RNA, triple helix, dominant-negative mutants, and various compounds reducing ligand availability. The experience with these strategies combined with the knowledge gained with current anti-growth factor receptor drugs should streamline the development of anti-IGF-IR therapeutics.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
29
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6589-97
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Growth factor receptors as therapeutic targets: strategies to inhibit the insulin-like growth factor I receptor.
pubmed:affiliation
Kimmel Cancer Center, Thomas Jefferson University, 233 S 10th St., BLSB 631, Philadelphia, PA 19107, USA. eva.surmacz@mail.tju.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Review