Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2002-5-28
pubmed:abstractText
Rapamycins represent a novel family of anticancer agents, currently including rapamycin and its derivatives, CCI-779 and RAD001. Rapamycins inhibit the function of the mammalian target of rapamycin (mTOR), and potently suppress tumor cell growth by arresting cells in G1 phase or potentially inducing apoptosis of cells, in culture or in xenograft tumor models. However, recent data indicate that genetic mutations or compensatory changes in tumor cells influence the sensitivity of rapamycins. First, mutations of mTOR or FKBP12 prevent rapamycin from binding to mTOR, conferring rapamycin resistance. Second, mutations or defects of mTOR-regulated proteins, including S6K1, 4E-BP1, PP2A-related phosphatases, and p27(Kip1) also render rapamycin insensitivity. In addition, the status of ATM, p53, PTEN/Akt and 14-3-3 are also associated with rapamycin sensitivity. To better explore the role of rapamycins against tumors, this review will summarize the current knowledge of the mechanism of action of rapamycins, and progress in understanding mechanisms of acquired or intrinsic resistance.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing, http://linkedlifedata.com/resource/pubmed/chemical/Antibiotics, Antineoplastic, http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins, http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Fungal Proteins, http://linkedlifedata.com/resource/pubmed/chemical/MTOR protein, human, http://linkedlifedata.com/resource/pubmed/chemical/PTEN Phosphohydrolase, http://linkedlifedata.com/resource/pubmed/chemical/PTEN protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Phosphoric Monoester Hydrolases, http://linkedlifedata.com/resource/pubmed/chemical/Proliferating Cell Nuclear Antigen, http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Saccharomyces cerevisiae Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Sirolimus, http://linkedlifedata.com/resource/pubmed/chemical/TAP42 protein, S cerevisiae, http://linkedlifedata.com/resource/pubmed/chemical/TOR Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Tacrolimus Binding Protein 1A, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins, http://linkedlifedata.com/resource/pubmed/chemical/ataxia telangiectasia mutated..., http://linkedlifedata.com/resource/pubmed/chemical/p27 antigen
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1368-7646
pubmed:author
pubmed:copyrightInfo
Copyright 2002 Elsevier Science Ltd.
pubmed:issnType
Print
pubmed:volume
4
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
378-91
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed-meshheading:12030785-Adaptor Proteins, Signal Transducing, pubmed-meshheading:12030785-Animals, pubmed-meshheading:12030785-Antibiotics, Antineoplastic, pubmed-meshheading:12030785-Apoptosis, pubmed-meshheading:12030785-Cell Cycle Proteins, pubmed-meshheading:12030785-DNA-Binding Proteins, pubmed-meshheading:12030785-Drug Resistance, Neoplasm, pubmed-meshheading:12030785-Fungal Proteins, pubmed-meshheading:12030785-Genes, p53, pubmed-meshheading:12030785-Humans, pubmed-meshheading:12030785-Mutation, pubmed-meshheading:12030785-PTEN Phosphohydrolase, pubmed-meshheading:12030785-Phosphoric Monoester Hydrolases, pubmed-meshheading:12030785-Proliferating Cell Nuclear Antigen, pubmed-meshheading:12030785-Protein Kinases, pubmed-meshheading:12030785-Protein-Serine-Threonine Kinases, pubmed-meshheading:12030785-Saccharomyces cerevisiae Proteins, pubmed-meshheading:12030785-Sirolimus, pubmed-meshheading:12030785-TOR Serine-Threonine Kinases, pubmed-meshheading:12030785-Tacrolimus Binding Protein 1A, pubmed-meshheading:12030785-Tumor Suppressor Proteins
pubmed:year
2001
pubmed:articleTitle
Mechanisms of resistance to rapamycins.
pubmed:affiliation
Department of Molecular Pharmacology, St. Jude Children's Research Hospital, Memphis, TN 38105-2794, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Review, Research Support, Non-U.S. Gov't