Cited 19 times in
Antitumor Activity and Acquired Resistance Mechanism of Dovitinib (TKI258) in RET-Rearranged Lung Adenocarcinoma
DC Field | Value | Language |
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dc.contributor.author | 강찬우 | - |
dc.contributor.author | 강한나 | - |
dc.contributor.author | 김대준 | - |
dc.contributor.author | 김주항 | - |
dc.contributor.author | 김혜련 | - |
dc.contributor.author | 김환 | - |
dc.contributor.author | 문용화 | - |
dc.contributor.author | 백순명 | - |
dc.contributor.author | 윤미란 | - |
dc.contributor.author | 임선민 | - |
dc.contributor.author | 장강원 | - |
dc.contributor.author | 조병철 | - |
dc.contributor.author | 표경호 | - |
dc.date.accessioned | 2018-03-26T16:56:20Z | - |
dc.date.available | 2018-03-26T16:56:20Z | - |
dc.date.issued | 2015 | - |
dc.identifier.issn | 1535-7163 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/156983 | - |
dc.description.abstract | RET rearrangement is a newly identified oncogenic mutation in lung adenocarcinoma (LADC). Activity of dovitinib (TKI258), a potent inhibitor of FGFR, VEGFR, and PDGFR, in RET-rearranged LADC has not been reported. The aims of the study are to explore antitumor effects and mechanisms of acquired resistance of dovitinib in RET-rearranged LADC. Using structural modeling and in vitro analysis, we demonstrated that dovitinib induced cell-cycle arrest at G0-G1 phase and apoptosis by selective inhibition of RET kinase activity and ERK1/2 signaling in RET-rearranged LC-2/ad cells. Strong antitumor effect of dovitinib was observed in an LC-2/ad tumor xenograft model. To identify the acquired resistance mechanisms to dovitinib, LC-2/ad cells were exposed to increasing concentrations of dovitinib to generate LC-2/ad DR cells. Gene-set enrichment analysis of gene expression and phosphor-kinase revealed that Src, a central gene in focal adhesion, was activated in LC-2/ad DR cells. Saracatinib, an src kinase inhibitor, suppressed ERK1/2 phosphorylation and growth of LC-2/ad DR cells. Taken together, these findings suggest that dovitinib can be a potential therapeutic option for RET-rearranged LADC, in which acquired resistance to dovitinib can be overcome by targeting Src. | - |
dc.description.statementOfResponsibility | open | - |
dc.language | English | - |
dc.publisher | American Association for Cancer Research | - |
dc.relation.isPartOf | MOLECULAR CANCER THERAPEUTICS | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Adenocarcinoma/drug therapy* | - |
dc.subject.MESH | Adenocarcinoma/enzymology | - |
dc.subject.MESH | Adenocarcinoma/pathology | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Antineoplastic Agents/chemistry | - |
dc.subject.MESH | Antineoplastic Agents/pharmacology* | - |
dc.subject.MESH | Apoptosis | - |
dc.subject.MESH | Benzimidazoles/chemistry | - |
dc.subject.MESH | Benzimidazoles/pharmacology* | - |
dc.subject.MESH | Catalytic Domain | - |
dc.subject.MESH | Cell Cycle Checkpoints | - |
dc.subject.MESH | Cell Line, Tumor | - |
dc.subject.MESH | Drug Resistance, Neoplasm* | - |
dc.subject.MESH | Enzyme Activation | - |
dc.subject.MESH | HEK293 Cells | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Inhibitory Concentration 50 | - |
dc.subject.MESH | Lung Neoplasms/drug therapy* | - |
dc.subject.MESH | Lung Neoplasms/enzymology | - |
dc.subject.MESH | Lung Neoplasms/pathology | - |
dc.subject.MESH | Mice, Nude | - |
dc.subject.MESH | Models, Molecular | - |
dc.subject.MESH | Protein Kinase Inhibitors | - |
dc.subject.MESH | Proto-Oncogene Proteins c-ret/antagonists & inhibitors* | - |
dc.subject.MESH | Proto-Oncogene Proteins c-ret/chemistry | - |
dc.subject.MESH | Quinolones/chemistry | - |
dc.subject.MESH | Quinolones/pharmacology* | - |
dc.subject.MESH | Tumor Burden/drug effects | - |
dc.subject.MESH | Xenograft Model Antitumor Assays | - |
dc.subject.MESH | src-Family Kinases/metabolism | - |
dc.title | Antitumor Activity and Acquired Resistance Mechanism of Dovitinib (TKI258) in RET-Rearranged Lung Adenocarcinoma | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine | - |
dc.contributor.department | Yonsei Biomedical Research Center | - |
dc.contributor.googleauthor | Chan Woo Kang | - |
dc.contributor.googleauthor | Kang Won Jang | - |
dc.contributor.googleauthor | Jinyoung Sohn | - |
dc.contributor.googleauthor | Sung-Moo Kim | - |
dc.contributor.googleauthor | Kyoung-Ho Pyo | - |
dc.contributor.googleauthor | Hwan Kim | - |
dc.contributor.googleauthor | Mi Ran Yun | - |
dc.contributor.googleauthor | Han Na Kang | - |
dc.contributor.googleauthor | Hye Ryun Kim | - |
dc.contributor.googleauthor | Sun Min Lim | - |
dc.contributor.googleauthor | Yong Wha Moon | - |
dc.contributor.googleauthor | Soonmyung Paik | - |
dc.contributor.googleauthor | Dae Joon Kim | - |
dc.contributor.googleauthor | Joo Hang Kim | - |
dc.contributor.googleauthor | Byoung Chul Cho | - |
dc.identifier.doi | 10.1158/1535-7163.MCT-15-0350 | - |
dc.contributor.localId | A00087 | - |
dc.contributor.localId | A05081 | - |
dc.contributor.localId | A00368 | - |
dc.contributor.localId | A00945 | - |
dc.contributor.localId | A01166 | - |
dc.contributor.localId | A05117 | - |
dc.contributor.localId | A01370 | - |
dc.contributor.localId | A01823 | - |
dc.contributor.localId | A04776 | - |
dc.contributor.localId | A03369 | - |
dc.contributor.localId | A03421 | - |
dc.contributor.localId | A03822 | - |
dc.contributor.localId | A04809 | - |
dc.relation.journalcode | J02254 | - |
dc.identifier.eissn | 1538-8514 | - |
dc.identifier.pmid | 26208525 | - |
dc.contributor.alternativeName | Kang, Chan Woo | - |
dc.contributor.alternativeName | Kang, Han Na | - |
dc.contributor.alternativeName | Kim, Dae Joon | - |
dc.contributor.alternativeName | Kim, Joo Hang | - |
dc.contributor.alternativeName | Kim, Hye Ryun | - |
dc.contributor.alternativeName | Kim, Hwan | - |
dc.contributor.alternativeName | Moon, Yong Wha | - |
dc.contributor.alternativeName | Paik, Soon Myung | - |
dc.contributor.alternativeName | Yun, Mi Ran | - |
dc.contributor.alternativeName | Lim, Sun Min | - |
dc.contributor.alternativeName | Jang, Kang Won | - |
dc.contributor.alternativeName | Cho, Byoung Chul | - |
dc.contributor.alternativeName | Pyo, Kyoung Ho | - |
dc.contributor.affiliatedAuthor | Kang, Chan Woo | - |
dc.contributor.affiliatedAuthor | Kang, Han Na | - |
dc.contributor.affiliatedAuthor | Kim, Dae Joon | - |
dc.contributor.affiliatedAuthor | Kim, Joo Hang | - |
dc.contributor.affiliatedAuthor | Kim, Hye Ryun | - |
dc.contributor.affiliatedAuthor | Kim, Hwan | - |
dc.contributor.affiliatedAuthor | Moon, Yong Wha | - |
dc.contributor.affiliatedAuthor | Paik, Soon Myung | - |
dc.contributor.affiliatedAuthor | Yun, Mi Ran | - |
dc.contributor.affiliatedAuthor | Lim, Sun Min | - |
dc.contributor.affiliatedAuthor | Jang, Kang Won | - |
dc.contributor.affiliatedAuthor | Cho, Byoung Chul | - |
dc.contributor.affiliatedAuthor | Pyo, Kyoung Ho | - |
dc.citation.volume | 14 | - |
dc.citation.number | 10 | - |
dc.citation.startPage | 2238 | - |
dc.citation.endPage | 2248 | - |
dc.identifier.bibliographicCitation | MOLECULAR CANCER THERAPEUTICS, Vol.14(10) : 2238-2248, 2015 | - |
dc.identifier.rimsid | 41292 | - |
dc.type.rims | ART | - |
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