Matches in SemOpenAlex for { <https://semopenalex.org/work/W2082779498> ?p ?o ?g. }
- W2082779498 endingPage "1620" @default.
- W2082779498 startingPage "1610" @default.
- W2082779498 abstract "Abstract Recent evidence implicates the insulin-like growth factor (IGF) pathway in development of Ewing sarcoma, a highly malignant bone and soft-tissue tumor that primarily affects children and young adults. Despite promising results from preclinical studies of therapies that target this pathway, early-phase clinical trials have shown that a significant fraction of patients do not benefit, suggesting that cellular factors determine tumor sensitivity. Using FAIRE-seq, a chromosomal deletion of the PTEN locus in a Ewing sarcoma cell line was identified. In primary tumors, PTEN deficiency was observed in a large subset of cases, although not mediated by large chromosomal deletions. PTEN loss resulted in hyperactivation of the AKT signaling pathway. PTEN rescue led to decreased proliferation, inhibition of colony formation, and increased apoptosis. Strikingly, PTEN loss decreased sensitivity to IGF1R inhibitors but increased responsiveness to temsirolimus, a potent mTOR inhibitor, as marked by induction of autophagy. These results suggest that PTEN is lost in a significant fraction of primary tumors, and this deficiency may have therapeutic consequences by concurrently attenuating responsiveness to IGF1R inhibition while increasing activity of mTOR inhibitors. The identification of PTEN status in the tumors of patients with recurrent disease could help guide the selection of therapies. Implications: PTEN status in Ewing sarcoma affects cellular responses to IGFI and mTOR-directed therapy, thus justifying its consideration as a biomarker in future clinical trials. Mol Cancer Res; 12(11); 1610–20. ©2014 AACR." @default.
- W2082779498 created "2016-06-24" @default.
- W2082779498 creator A5001832821 @default.
- W2082779498 creator A5002083919 @default.
- W2082779498 creator A5019187002 @default.
- W2082779498 creator A5029824016 @default.
- W2082779498 creator A5041437800 @default.
- W2082779498 creator A5041976491 @default.
- W2082779498 creator A5042672225 @default.
- W2082779498 creator A5046980356 @default.
- W2082779498 creator A5058731927 @default.
- W2082779498 creator A5071271041 @default.
- W2082779498 creator A5090336291 @default.
- W2082779498 date "2014-11-01" @default.
- W2082779498 modified "2023-09-26" @default.
- W2082779498 title "PTEN Deficiency Mediates a Reciprocal Response to IGFI and mTOR Inhibition" @default.
- W2082779498 cites W1964171663 @default.
- W2082779498 cites W1965261779 @default.
- W2082779498 cites W1972809568 @default.
- W2082779498 cites W1977767269 @default.
- W2082779498 cites W1982238847 @default.
- W2082779498 cites W1986384280 @default.
- W2082779498 cites W1986799557 @default.
- W2082779498 cites W1987005520 @default.
- W2082779498 cites W1991236371 @default.
- W2082779498 cites W1993308254 @default.
- W2082779498 cites W1999030960 @default.
- W2082779498 cites W2000646653 @default.
- W2082779498 cites W2006846985 @default.
- W2082779498 cites W2007374710 @default.
- W2082779498 cites W2016274355 @default.
- W2082779498 cites W2021466588 @default.
- W2082779498 cites W2037018303 @default.
- W2082779498 cites W2044313879 @default.
- W2082779498 cites W2054711858 @default.
- W2082779498 cites W2058759427 @default.
- W2082779498 cites W2059514034 @default.
- W2082779498 cites W2061054148 @default.
- W2082779498 cites W2063249691 @default.
- W2082779498 cites W2068427129 @default.
- W2082779498 cites W2069351898 @default.
- W2082779498 cites W2071609853 @default.
- W2082779498 cites W2078576279 @default.
- W2082779498 cites W2078689449 @default.
- W2082779498 cites W2080100938 @default.
- W2082779498 cites W2081994535 @default.
- W2082779498 cites W2082138815 @default.
- W2082779498 cites W2083987452 @default.
- W2082779498 cites W2095686972 @default.
- W2082779498 cites W2096113686 @default.
- W2082779498 cites W2099187439 @default.
- W2082779498 cites W2101722758 @default.
- W2082779498 cites W2102388598 @default.
- W2082779498 cites W2102820712 @default.
- W2082779498 cites W2106972520 @default.
- W2082779498 cites W2107596018 @default.
- W2082779498 cites W2113168035 @default.
- W2082779498 cites W2118262694 @default.
- W2082779498 cites W2128271300 @default.
- W2082779498 cites W2135398049 @default.
- W2082779498 cites W2135433020 @default.
- W2082779498 cites W2141398932 @default.
- W2082779498 cites W2145088312 @default.
- W2082779498 cites W2151503957 @default.
- W2082779498 cites W2159876545 @default.
- W2082779498 cites W2159990074 @default.
- W2082779498 cites W2161810908 @default.
- W2082779498 cites W2170407716 @default.
- W2082779498 cites W2388163742 @default.
- W2082779498 cites W4255221283 @default.
- W2082779498 doi "https://doi.org/10.1158/1541-7786.mcr-14-0006" @default.
- W2082779498 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4233155" @default.
- W2082779498 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24994750" @default.
- W2082779498 hasPublicationYear "2014" @default.
- W2082779498 type Work @default.
- W2082779498 sameAs 2082779498 @default.
- W2082779498 citedByCount "21" @default.
- W2082779498 countsByYear W20827794982014 @default.
- W2082779498 countsByYear W20827794982015 @default.
- W2082779498 countsByYear W20827794982016 @default.
- W2082779498 countsByYear W20827794982017 @default.
- W2082779498 countsByYear W20827794982019 @default.
- W2082779498 countsByYear W20827794982020 @default.
- W2082779498 countsByYear W20827794982021 @default.
- W2082779498 countsByYear W20827794982022 @default.
- W2082779498 countsByYear W20827794982023 @default.
- W2082779498 crossrefType "journal-article" @default.
- W2082779498 hasAuthorship W2082779498A5001832821 @default.
- W2082779498 hasAuthorship W2082779498A5002083919 @default.
- W2082779498 hasAuthorship W2082779498A5019187002 @default.
- W2082779498 hasAuthorship W2082779498A5029824016 @default.
- W2082779498 hasAuthorship W2082779498A5041437800 @default.
- W2082779498 hasAuthorship W2082779498A5041976491 @default.
- W2082779498 hasAuthorship W2082779498A5042672225 @default.
- W2082779498 hasAuthorship W2082779498A5046980356 @default.
- W2082779498 hasAuthorship W2082779498A5058731927 @default.
- W2082779498 hasAuthorship W2082779498A5071271041 @default.
- W2082779498 hasAuthorship W2082779498A5090336291 @default.