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Anti-tumor effects of NVP-BKM120 alone or in combination with MEK162 in biliary tract cancer
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Jin, Ling | - |
dc.contributor.author | Jin, Mei-hua | - |
dc.contributor.author | Nam, Ah-Rong | - |
dc.contributor.author | Park, Ji-Eun | - |
dc.contributor.author | Bang, Ju-Hee | - |
dc.contributor.author | Oh, Do Yeun | - |
dc.contributor.author | Bang, Yung Jue | - |
dc.date.accessioned | 2021-01-31T11:58:08Z | - |
dc.date.available | 2021-01-31T11:58:08Z | - |
dc.date.created | 2018-06-05 | - |
dc.date.issued | 2017-12 | - |
dc.identifier.citation | Cancer Letters, Vol.411, pp.162-170 | - |
dc.identifier.issn | 0304-3835 | - |
dc.identifier.other | 37104 | - |
dc.identifier.uri | https://hdl.handle.net/10371/173169 | - |
dc.description.abstract | There are currently no clinically validated therapeutic targets for biliary tract cancer (BTC). Despite promising results in other cancers, compounds targeting the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, alone or in combination with Ras/Raf/MEK pathway inhibitors, have not been evaluated in BTC. Here, we examined the effects of a pan-PI3K inhibitor (BKM120) with or without a MEK inhibitor (MEK162), on eight human BTC cell lines carrying mutations in K-Ras and/or the PI3K catalytic subunit, P13KCA. BKM120 inhibited the colony-forming ability and migration of BTC cells carrying wild-type (WT) PI3KCA and either mutant (MT) or WT K-Ras, but not of cells carrying mutations in both genes. In K-Ras-WT cells, BKM120 decreased the phosphorylation of Akt, its downstream effector kinase p70S6K, and the translational repressor 4E-BP1. Interestingly, BKM120 did not induce cell cycle arrest or suppress PI3K signaling via restoration of p-4E-BP1 in cells with PIK3CA and K-Ras double mutations. Notably, the resistance of dual K-Ras/PI3KCA-mutant cells to BKM120 was overcome by treatment with a combination of BKM120 and MEK162. Our findings thus support the clinical development of BKM120 monotherapy or BKM120/MEK162 combination therapy for the treatment of BTC. (c) 2017 Elsevier B.V. All rights reserved. | - |
dc.language | 영어 | - |
dc.publisher | Elsevier BV | - |
dc.title | Anti-tumor effects of NVP-BKM120 alone or in combination with MEK162 in biliary tract cancer | - |
dc.type | Article | - |
dc.contributor.AlternativeAuthor | 방영주 | - |
dc.identifier.doi | 10.1016/j.canlet.2017.10.002 | - |
dc.citation.journaltitle | Cancer Letters | - |
dc.identifier.wosid | 000416299700019 | - |
dc.identifier.scopusid | 2-s2.0-85031774673 | - |
dc.citation.endpage | 170 | - |
dc.citation.startpage | 162 | - |
dc.citation.volume | 411 | - |
dc.identifier.sci | 000416299700019 | - |
dc.description.isOpenAccess | N | - |
dc.contributor.affiliatedAuthor | Oh, Do Yeun | - |
dc.contributor.affiliatedAuthor | Bang, Yung Jue | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | PATHWAY INHIBITORS | - |
dc.subject.keywordPlus | BREAST-CANCER | - |
dc.subject.keywordPlus | RESISTANCE | - |
dc.subject.keywordPlus | PI3K | - |
dc.subject.keywordPlus | CHOLANGIOCARCINOMA | - |
dc.subject.keywordPlus | OVEREXPRESSION | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | MUTATIONS | - |
dc.subject.keywordPlus | THERAPY | - |
dc.subject.keywordPlus | CELLS | - |
dc.subject.keywordAuthor | PI3K inhibitor | - |
dc.subject.keywordAuthor | MEK inhibitor | - |
dc.subject.keywordAuthor | K-Ras | - |
dc.subject.keywordAuthor | Biliary tract cancer | - |
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