Linked Life Data

15584862

Source:http://linkedlifedata.com/resource/pubmed/id/15584862

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2004-12-8
pubmed:abstractText
Target of rapamycin (TOR) functions within the cell as a transducer of information from various sources, including growth factors, energy sensors, and hypoxia sensors, as well as components of the cell regulating growth and division. Blocking TOR function mimics amino acid, and to some extent, growth factor deprivation and has a cytostatic effect on proliferating cells in vivo. Inhibition of TOR in vivo, utilising its namesake rapamycin, leads to immunosuppression. This property has been exploited successfully with the use of rapamycin and its derivatives as a therapeutic agent in the prevention of organ rejection after transplantation with relatively mild side effects when compared to other immunosuppressive agents. The cytostatic effect of TOR on vascular smooth muscle cell proliferation has also recently been exploited in the therapeutic application of rapamycin to drug eluting stents for angioplasty. These stents significantly reduce the amount of arterial reblockage that results from proliferating vascular smooth muscle cells. In cancer, the effect of blocking TOR function on tumour growth and disease progression is currently of major interest and is the basis for a number of ongoing clinical trials. However, different cell types and tumours respond differently to TOR inhibition, and TOR is clearly not cytostatic for all types of cancer cells in vitro or in vivo. As the molecular details of how TOR functions and the targets of TOR activity are further elucidated, tumour and tissue specific functions are being identified that implicate TOR in angiogenesis, apoptosis, and the reversal of some forms of cellular transformation. This review will describe our current understanding of TOR function, describe the current strategies for employing TOR inhibitors in clinical and preclinical development, and outline future strategies for appropriate targets of TOR inhibitors in the treatment of disease.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1744-7631
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
551-64
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:15584862-Antineoplastic Agents, pubmed-meshheading:15584862-Apoptosis, pubmed-meshheading:15584862-Arterial Occlusive Diseases, pubmed-meshheading:15584862-Cell Division, pubmed-meshheading:15584862-Clinical Trials as Topic, pubmed-meshheading:15584862-Energy Metabolism, pubmed-meshheading:15584862-Gene Expression Regulation, pubmed-meshheading:15584862-Growth Substances, pubmed-meshheading:15584862-Heart Transplantation, pubmed-meshheading:15584862-Humans, pubmed-meshheading:15584862-Immunosuppressive Agents, pubmed-meshheading:15584862-Models, Biological, pubmed-meshheading:15584862-Muscle, Smooth, Vascular, pubmed-meshheading:15584862-Neoplasm Proteins, pubmed-meshheading:15584862-Neoplasms, pubmed-meshheading:15584862-Neovascularization, Pathologic, pubmed-meshheading:15584862-Postoperative Complications, pubmed-meshheading:15584862-Protein Kinase Inhibitors, pubmed-meshheading:15584862-Protein Kinases, pubmed-meshheading:15584862-Protein Structure, Tertiary, pubmed-meshheading:15584862-Signal Transduction, pubmed-meshheading:15584862-Sirolimus, pubmed-meshheading:15584862-Stents, pubmed-meshheading:15584862-TOR Serine-Threonine Kinases, pubmed-meshheading:15584862-Wound Healing
pubmed:year
2004
pubmed:articleTitle
Therapeutic potential of target of rapamycin inhibitors.
pubmed:affiliation
St. Jude Childrens Research Hospital, Department of Molecular Pharmacology, 332 N. Lauderdale Street, Memphis, TN 38105-2794, USA.
pubmed:publicationType
Journal Article, Review