FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2169663847> ?p ?o ?g. }

• W2169663847 endingPage "1073" @default.
• W2169663847 startingPage "1062" @default.
• W2169663847 abstract "Abstract NF1 encodes a RAS GTPase-activating protein. Accordingly, aberrant RAS activation underlies the pathogenesis of NF1-mutant cancers. Nevertheless, it is unclear which RAS pathway components represent optimal therapeutic targets. Here, we identify mTORC1 as the key PI3K effector in NF1-mutant nervous system malignancies and conversely show that mTORC2 and AKT are dispensable. However, we find that tumor regression requires sustained inhibition of both mTORC1 and MEK. Transcriptional profiling studies were therefore used to establish a signature of effective mTORC1–MEK inhibition in vivo. We unexpectedly found that the glucose transporter GLUT1 was potently suppressed, but only when both pathways were inhibited. Moreover, unlike VHL- and LKB1-mutant cancers, reduction of 18F-FDG uptake required the suppression of both mTORC1 and MEK. Together, these studies identify optimal and suboptimal therapeutic targets in NF1-mutant malignancies and define a noninvasive means of measuring combined mTORC1–MEK inhibition in vivo, which can be readily incorporated into clinical trials. Significance: This work demonstrates that mTORC1 and MEK are key therapeutic targets in NF1-mutant cancers and establishes a noninvasive biomarker of effective, combined target inhibition that can be evaluated in clinical trials. Cancer Discov; 4(9); 1062–73. ©2014 AACR. This article is highlighted in the In This Issue feature, p. 973" @default.
• W2169663847 created "2016-06-24" @default.
• W2169663847 creator A5007309738 @default.
• W2169663847 creator A5007351308 @default.
• W2169663847 creator A5012167814 @default.
• W2169663847 creator A5043073689 @default.
• W2169663847 creator A5044913280 @default.
• W2169663847 creator A5091090936 @default.
• W2169663847 date "2014-09-01" @default.
• W2169663847 modified "2023-10-16" @default.
• W2169663847 title "Defining Key Signaling Nodes and Therapeutic Biomarkers in <i>NF1</i>-Mutant Cancers" @default.
• W2169663847 cites W1550997731 @default.
• W2169663847 cites W1574898460 @default.
• W2169663847 cites W1973307365 @default.
• W2169663847 cites W1976009942 @default.
• W2169663847 cites W1977420876 @default.
• W2169663847 cites W1979159394 @default.
• W2169663847 cites W1981711832 @default.
• W2169663847 cites W1998782296 @default.
• W2169663847 cites W2010729236 @default.
• W2169663847 cites W2014782980 @default.
• W2169663847 cites W2015408838 @default.
• W2169663847 cites W2018996650 @default.
• W2169663847 cites W2022971724 @default.
• W2169663847 cites W2025786205 @default.
• W2169663847 cites W2027971058 @default.
• W2169663847 cites W2029754521 @default.
• W2169663847 cites W2039924299 @default.
• W2169663847 cites W2040742535 @default.
• W2169663847 cites W2040827479 @default.
• W2169663847 cites W2041181609 @default.
• W2169663847 cites W2042612710 @default.
• W2169663847 cites W2055729102 @default.
• W2169663847 cites W2056111473 @default.
• W2169663847 cites W2056310329 @default.
• W2169663847 cites W2065322400 @default.
• W2169663847 cites W2065887259 @default.
• W2169663847 cites W2072478579 @default.
• W2169663847 cites W2073355522 @default.
• W2169663847 cites W2075997152 @default.
• W2169663847 cites W2077203214 @default.
• W2169663847 cites W2087693130 @default.
• W2169663847 cites W2096046981 @default.
• W2169663847 cites W2099257982 @default.
• W2169663847 cites W2126570100 @default.
• W2169663847 cites W2129172946 @default.
• W2169663847 cites W2130986759 @default.
• W2169663847 cites W2133403796 @default.
• W2169663847 cites W2134947634 @default.
• W2169663847 cites W2136923108 @default.
• W2169663847 cites W2137036286 @default.
• W2169663847 cites W2138616826 @default.
• W2169663847 cites W2139802897 @default.
• W2169663847 cites W2142317845 @default.
• W2169663847 cites W2152600551 @default.
• W2169663847 cites W2156760370 @default.
• W2169663847 cites W2159750196 @default.
• W2169663847 cites W2163798887 @default.
• W2169663847 cites W2170842763 @default.
• W2169663847 cites W4238567307 @default.
• W2169663847 cites W65115710 @default.
• W2169663847 doi "https://doi.org/10.1158/2159-8290.cd-14-0159" @default.
• W2169663847 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4446704" @default.
• W2169663847 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24913553" @default.
• W2169663847 hasPublicationYear "2014" @default.
• W2169663847 type Work @default.
• W2169663847 sameAs 2169663847 @default.
• W2169663847 citedByCount "50" @default.
• W2169663847 countsByYear W21696638472015 @default.
• W2169663847 countsByYear W21696638472016 @default.
• W2169663847 countsByYear W21696638472017 @default.
• W2169663847 countsByYear W21696638472018 @default.
• W2169663847 countsByYear W21696638472019 @default.
• W2169663847 countsByYear W21696638472020 @default.
• W2169663847 countsByYear W21696638472021 @default.
• W2169663847 countsByYear W21696638472022 @default.
• W2169663847 countsByYear W21696638472023 @default.
• W2169663847 crossrefType "journal-article" @default.
• W2169663847 hasAuthorship W2169663847A5007309738 @default.
• W2169663847 hasAuthorship W2169663847A5007351308 @default.
• W2169663847 hasAuthorship W2169663847A5012167814 @default.
• W2169663847 hasAuthorship W2169663847A5043073689 @default.
• W2169663847 hasAuthorship W2169663847A5044913280 @default.
• W2169663847 hasAuthorship W2169663847A5091090936 @default.
• W2169663847 hasBestOaLocation W21696638471 @default.
• W2169663847 hasConcept C104317684 @default.
• W2169663847 hasConcept C121608353 @default.
• W2169663847 hasConcept C143065580 @default.
• W2169663847 hasConcept C170932241 @default.
• W2169663847 hasConcept C502942594 @default.
• W2169663847 hasConcept C51785407 @default.
• W2169663847 hasConcept C54355233 @default.
• W2169663847 hasConcept C62478195 @default.
• W2169663847 hasConcept C86554907 @default.
• W2169663847 hasConcept C86803240 @default.
• W2169663847 hasConcept C95444343 @default.
• W2169663847 hasConcept C98490376 @default.
• W2169663847 hasConceptScore W2169663847C104317684 @default.

• next