Matches in SemOpenAlex for { <https://semopenalex.org/work/W2029278601> ?p ?o ?g. }
Showing items 1 to 88 of
88
with 100 items per page.
- W2029278601 abstract "Amplification of MYCN is associated with high-risk SHH-driven and group 4 medulloblastoma, while mis-expression and amplification of MYC is associated with aggressive group 3 tumors. The biology of these tumors, particularly the group 3/4 tumors, is poorly understood, with no effective targeted therapies. We have recently developed a model of group 4 medulloblastoma in which high levels of mutationally-stabilized MYCN protein drive oncogenesis. We have shown in other tumor types that modulation of the translational apparatus downstream of the mammalian target of rapamycin (mTOR) is required for MYC-driven oncogenesis and that there is a synergistic relationship between MYC and the mTOR axis to promote tumor formation. mTOR signals through two primary outputs, rpS6 kinase (S6K) and the translation initiation factor eIF4E. A new class of clinical mTOR active site inhibitors disrupts signaling through both effectors, whereas the allosteric binder rapamycin disrupts only S6K. We describe genetic and therapeutic studies aimed at distinguishing the effects of S6K and eIF4E in both tumor formation and in therapy. These mechanistically distinct activities have enormous therapeutic implications, as in our medulloblastoma model, active site inhibitors of mTOR, but not rapamycin, demonstrate efficacy. Taken together, this supports the idea that signaling through S6K is dispensable, whereas eIF4E is required for MYC-driven oncogenesis. Citation Format: Justin G. Meyerowitz, W. Clay Gustafson, Erin Nekritz, Fredrik Swartling, Kevan M. Shokat, Davide Ruggero, William A. Weiss. Targeting the translational apparatus in MYCN-driven medulloblastoma. [abstract]. In: Proceedings of the AACR Special Conference on Pediatric Cancer at the Crossroads: Translating Discovery into Improved Outcomes; Nov 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;74(20 Suppl):Abstract nr B78." @default.
- W2029278601 created "2016-06-24" @default.
- W2029278601 creator A5014596457 @default.
- W2029278601 creator A5022224678 @default.
- W2029278601 creator A5023731504 @default.
- W2029278601 creator A5068758660 @default.
- W2029278601 creator A5073603294 @default.
- W2029278601 creator A5079376363 @default.
- W2029278601 creator A5082896068 @default.
- W2029278601 date "2014-10-09" @default.
- W2029278601 modified "2023-09-25" @default.
- W2029278601 title "Abstract B78: Targeting the translational apparatus in MYCN-driven medulloblastoma" @default.
- W2029278601 doi "https://doi.org/10.1158/1538-7445.pedcan-b78" @default.
- W2029278601 hasPublicationYear "2014" @default.
- W2029278601 type Work @default.
- W2029278601 sameAs 2029278601 @default.
- W2029278601 citedByCount "0" @default.
- W2029278601 crossrefType "proceedings-article" @default.
- W2029278601 hasAuthorship W2029278601A5014596457 @default.
- W2029278601 hasAuthorship W2029278601A5022224678 @default.
- W2029278601 hasAuthorship W2029278601A5023731504 @default.
- W2029278601 hasAuthorship W2029278601A5068758660 @default.
- W2029278601 hasAuthorship W2029278601A5073603294 @default.
- W2029278601 hasAuthorship W2029278601A5079376363 @default.
- W2029278601 hasAuthorship W2029278601A5082896068 @default.
- W2029278601 hasConcept C104202773 @default.
- W2029278601 hasConcept C104317684 @default.
- W2029278601 hasConcept C105580179 @default.
- W2029278601 hasConcept C121608353 @default.
- W2029278601 hasConcept C149364088 @default.
- W2029278601 hasConcept C161295673 @default.
- W2029278601 hasConcept C2776715637 @default.
- W2029278601 hasConcept C2777956278 @default.
- W2029278601 hasConcept C2779102060 @default.
- W2029278601 hasConcept C2780789225 @default.
- W2029278601 hasConcept C502942594 @default.
- W2029278601 hasConcept C54355233 @default.
- W2029278601 hasConcept C555283112 @default.
- W2029278601 hasConcept C62478195 @default.
- W2029278601 hasConcept C81885089 @default.
- W2029278601 hasConcept C86554907 @default.
- W2029278601 hasConcept C86803240 @default.
- W2029278601 hasConcept C95444343 @default.
- W2029278601 hasConceptScore W2029278601C104202773 @default.
- W2029278601 hasConceptScore W2029278601C104317684 @default.
- W2029278601 hasConceptScore W2029278601C105580179 @default.
- W2029278601 hasConceptScore W2029278601C121608353 @default.
- W2029278601 hasConceptScore W2029278601C149364088 @default.
- W2029278601 hasConceptScore W2029278601C161295673 @default.
- W2029278601 hasConceptScore W2029278601C2776715637 @default.
- W2029278601 hasConceptScore W2029278601C2777956278 @default.
- W2029278601 hasConceptScore W2029278601C2779102060 @default.
- W2029278601 hasConceptScore W2029278601C2780789225 @default.
- W2029278601 hasConceptScore W2029278601C502942594 @default.
- W2029278601 hasConceptScore W2029278601C54355233 @default.
- W2029278601 hasConceptScore W2029278601C555283112 @default.
- W2029278601 hasConceptScore W2029278601C62478195 @default.
- W2029278601 hasConceptScore W2029278601C81885089 @default.
- W2029278601 hasConceptScore W2029278601C86554907 @default.
- W2029278601 hasConceptScore W2029278601C86803240 @default.
- W2029278601 hasConceptScore W2029278601C95444343 @default.
- W2029278601 hasLocation W20292786011 @default.
- W2029278601 hasOpenAccess W2029278601 @default.
- W2029278601 hasPrimaryLocation W20292786011 @default.
- W2029278601 hasRelatedWork W1514463021 @default.
- W2029278601 hasRelatedWork W2012731742 @default.
- W2029278601 hasRelatedWork W2071831626 @default.
- W2029278601 hasRelatedWork W2084669819 @default.
- W2029278601 hasRelatedWork W2151748280 @default.
- W2029278601 hasRelatedWork W2316282661 @default.
- W2029278601 hasRelatedWork W2338340854 @default.
- W2029278601 hasRelatedWork W2461272518 @default.
- W2029278601 hasRelatedWork W2465661011 @default.
- W2029278601 hasRelatedWork W2474705352 @default.
- W2029278601 hasRelatedWork W2504837974 @default.
- W2029278601 hasRelatedWork W2612472373 @default.
- W2029278601 hasRelatedWork W2741270174 @default.
- W2029278601 hasRelatedWork W2948785548 @default.
- W2029278601 hasRelatedWork W2954552978 @default.
- W2029278601 hasRelatedWork W3046994859 @default.
- W2029278601 hasRelatedWork W3047040853 @default.
- W2029278601 hasRelatedWork W3127455220 @default.
- W2029278601 hasRelatedWork W3128122465 @default.
- W2029278601 hasRelatedWork W3130503619 @default.
- W2029278601 isParatext "false" @default.
- W2029278601 isRetracted "false" @default.
- W2029278601 magId "2029278601" @default.
- W2029278601 workType "article" @default.