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유전체교정연구단
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Sensitivity towards HDAC inhibition is associated with RTK/MAPK pathway activation in gastric cancer

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dc.contributor.authorSeidlitz, Therese-
dc.contributor.authorSchmaeche, Tim-
dc.contributor.authorGarcia, Fernando-
dc.contributor.authorLee, Joon Ho-
dc.contributor.authorQin, Nan-
dc.contributor.authorKochall, Susan-
dc.contributor.authorFohgrub, Juliane-
dc.contributor.authorPauck, David-
dc.contributor.authorRothe, Alexander-
dc.contributor.authorBonkyoung Koo-
dc.contributor.authorWeitz, Juergen-
dc.contributor.authorRemke, Marc-
dc.contributor.authorMunoz, Javier-
dc.contributor.authorStange, Daniel E.-
dc.date.accessioned2023-01-27T00:38:23Z-
dc.date.available2023-01-27T00:38:23Z-
dc.date.created2022-09-28-
dc.date.issued2022-10-
dc.identifier.issn1757-4676-
dc.identifier.urihttps://pr.ibs.re.kr/handle/8788114/12825-
dc.description.abstractGastric cancer ranks the fifth most common and third leading cause of cancer-related deaths worldwide. Alterations in the RTK/MAPK, WNT, cell adhesion, TP53, TGF beta, NOTCH, and NF kappa B signaling pathways could be identified as main oncogenic drivers. A combination of altered pathways can be associated with molecular subtypes of gastric cancer. In order to generate model systems to study the impact of different pathway alterations in a defined genetic background, we generated three murine organoid models: a RAS-activated (Kras(G12D), Tp53(R172H)), a WNT-activated (Apc(fl/fl), Tp53(R172H)), and a diffuse (Cdh1(fl/fl), Apc(fl/fl)) model. These organoid models were morphologically and phenotypically diverse, differed in proteome expression signatures and possessed individual drug sensitivities. A differential vulnerability to RTK/MAPK pathway interference based on the different mitogenic drivers and according to the level of dependence on the pathway could be uncovered. Furthermore, an association between RTK/MAPK pathway activity and susceptibility to HDAC inhibition was observed. This finding was further validated in patient-derived organoids from gastric adenocarcinoma, thus identifying a novel treatment approach for RTK/MAPK pathway altered gastric cancer patients.-
dc.language영어-
dc.publisherWILEY-
dc.titleSensitivity towards HDAC inhibition is associated with RTK/MAPK pathway activation in gastric cancer-
dc.typeArticle-
dc.type.rimsART-
dc.identifier.wosid000843687300001-
dc.identifier.scopusid2-s2.0-85136520550-
dc.identifier.rimsid78820-
dc.contributor.affiliatedAuthorBonkyoung Koo-
dc.identifier.doi10.15252/emmm.202215705-
dc.identifier.bibliographicCitationEMBO MOLECULAR MEDICINE, v.14, no.10-
dc.relation.isPartOfEMBO MOLECULAR MEDICINE-
dc.citation.titleEMBO MOLECULAR MEDICINE-
dc.citation.volume14-
dc.citation.number10-
dc.description.journalClass1-
dc.description.journalClass1-
dc.description.isOpenAccessN-
dc.description.journalRegisteredClassscie-
dc.description.journalRegisteredClassscopus-
dc.relation.journalWebOfScienceCategoryMedicine, Research & Experimental-
dc.subject.keywordPlusCELL LUNG-CANCER-
dc.subject.keywordPlusSTEM-CELLS-
dc.subject.keywordPlusIN-VITRO-
dc.subject.keywordPlusRESISTANCE-
dc.subject.keywordPlusORGANOIDS-
dc.subject.keywordPlusMECHANISMS-
dc.subject.keywordPlusSURVIVAL-
dc.subject.keywordPlusSUBTYPES-
dc.subject.keywordPlusTHERAPY-
dc.subject.keywordPlusSTOMACH-
dc.subject.keywordAuthorgastric cancer-
dc.subject.keywordAuthorHDACi-
dc.subject.keywordAuthorMAPK-
dc.subject.keywordAuthororganoids-
Appears in Collections:
Center for Genome Engineering(유전체 교정 연구단) > 1. Journal Papers (저널논문)
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