Cited 45 times in
Co-clinical trials demonstrate predictive biomarkers for dovitinib, an FGFR inhibitor, in lung squamous cell carcinoma
DC Field | Value | Language |
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dc.contributor.author | 김은영 | - |
dc.contributor.author | 김진아 | - |
dc.contributor.author | 김혜련 | - |
dc.contributor.author | 백순명 | - |
dc.contributor.author | 심효섭 | - |
dc.contributor.author | 이진구 | - |
dc.contributor.author | 조병철 | - |
dc.contributor.author | 홍민희 | - |
dc.date.accessioned | 2018-07-20T07:33:09Z | - |
dc.date.available | 2018-07-20T07:33:09Z | - |
dc.date.issued | 2017 | - |
dc.identifier.issn | 0923-7534 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/160283 | - |
dc.description.abstract | Background: We conducted co-clinical trials in patient-derived xenograft (PDX) models to identify predictive biomarkers for the multikinase inhibitor dovitinib in lung squamous cell carcinoma (LSCC). Methods: The PDX01-02 were established from LSCC patients enrolled in the phase II trial of dovitinib (NCT01861197) and PDX03-05 were established from LSCC patients receiving surgery. These five PDX tumors were subjected to in vivo test of dovitinib efficacy, whole exome sequencing and gene expression profiling. Results: The PDX tumors recapitulate histopathological properties and maintain genomic characteristics of originating tumors. Concordant with clinical outcomes of the trial enrolled-LSCC patients, dovitinib produced substantial tumor regression in PDX-01 and PDX-05, whereas it resulted in tumor progression in PDX-02. PDX-03 and -04 also displayed poor antitumor efficacy to dovitinib. Mutational and genome-wide copy number profiles revealed no correlation between genomic alterations of FGFR1-3 and sensitivity to dovitinib. Of note, gene expression profiles revealed differentially expressed genes including FGF3 and FGF19 between PDX-01 and 05 and PDX-02-04. Pathway analysis identified two FGFR signaling-related gene sets, FGFR ligand binding/activation and SHC-mediated cascade pathway were substantially up-regulated in PDX-01 and 05, compared with PDX-02-04. The comparison of gene expression profiles between dovitinib-sensitive versus -resistant lung cancer cell lines in the Cancer Cell Line Encyclopedia database also found that transcriptional activation of 18 key signaling components in FGFR pathways can predict the sensitivity to dovitinib both in cell lines and PDX tumors. These results highlight FGFR pathway activation as a key molecular determinant for sensitivity to dovitinib. Conclusions: FGFR gene expression signatures are predictors for the response to dovitinib in LSCC. | - |
dc.description.statementOfResponsibility | restriction | - |
dc.language | English | - |
dc.publisher | Oxford University Press | - |
dc.relation.isPartOf | ANNALS OF ONCOLOGY | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Benzimidazoles/therapeutic use* | - |
dc.subject.MESH | Biomarkers/blood* | - |
dc.subject.MESH | Carcinoma, Squamous Cell/drug therapy* | - |
dc.subject.MESH | Carcinoma, Squamous Cell/genetics | - |
dc.subject.MESH | Clinical Trials as Topic* | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Lung Neoplasms/drug therapy* | - |
dc.subject.MESH | Lung Neoplasms/genetics Mutation | - |
dc.subject.MESH | Quinolones/therapeutic use* | - |
dc.subject.MESH | Receptors, Fibroblast Growth Factor/antagonists & inhibitors* | - |
dc.subject.MESH | Receptors, Fibroblast Growth Factor/metabolism | - |
dc.subject.MESH | Signal Transduction | - |
dc.subject.MESH | Whole Exome Sequencing | - |
dc.title | Co-clinical trials demonstrate predictive biomarkers for dovitinib, an FGFR inhibitor, in lung squamous cell carcinoma | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine | - |
dc.contributor.department | Dept. of Internal Medicine | - |
dc.contributor.googleauthor | H. R. Kim | - |
dc.contributor.googleauthor | H. N. Kang | - |
dc.contributor.googleauthor | H. S. Shim | - |
dc.contributor.googleauthor | E. Y. Kim | - |
dc.contributor.googleauthor | J. Kim | - |
dc.contributor.googleauthor | D. J. Kim | - |
dc.contributor.googleauthor | J. G. Lee | - |
dc.contributor.googleauthor | C. Y. Lee | - |
dc.contributor.googleauthor | M. H. Hong | - |
dc.contributor.googleauthor | S.-M. Kim | - |
dc.contributor.googleauthor | H. Kim | - |
dc.contributor.googleauthor | K.-H. Pyo | - |
dc.contributor.googleauthor | M. R. Yun | - |
dc.contributor.googleauthor | H. J. Park | - |
dc.contributor.googleauthor | J. Y. Han | - |
dc.contributor.googleauthor | H. A. Youn | - |
dc.contributor.googleauthor | M.-J. Ahn | - |
dc.contributor.googleauthor | S. Paik | - |
dc.contributor.googleauthor | T.-M. Kim | - |
dc.contributor.googleauthor | B. C. Cho | - |
dc.identifier.doi | 10.1093/annonc/mdx098 | - |
dc.contributor.localId | A00811 | - |
dc.contributor.localId | A01022 | - |
dc.contributor.localId | A01166 | - |
dc.contributor.localId | A01823 | - |
dc.contributor.localId | A02219 | - |
dc.contributor.localId | A03225 | - |
dc.contributor.localId | A03822 | - |
dc.contributor.localId | A04393 | - |
dc.relation.journalcode | J00171 | - |
dc.identifier.eissn | 1569-8041 | - |
dc.identifier.pmid | 28460066 | - |
dc.identifier.url | https://academic.oup.com/annonc/article/28/6/1250/3771561 | - |
dc.subject.keyword | biomarker | - |
dc.subject.keyword | dovitinib | - |
dc.subject.keyword | fibroblast growth factor receptor | - |
dc.subject.keyword | patient-derived xenograft | - |
dc.subject.keyword | squamous cell lung cancer | - |
dc.contributor.alternativeName | Kim, Eun Young | - |
dc.contributor.alternativeName | Kim, Jinna | - |
dc.contributor.alternativeName | Kim, Hye Ryun | - |
dc.contributor.alternativeName | Paik, Soon Myung | - |
dc.contributor.alternativeName | Shim, Hyo Sup | - |
dc.contributor.alternativeName | Lee, Jin Gu | - |
dc.contributor.alternativeName | Cho, Byoung Chul | - |
dc.contributor.alternativeName | Hong, Min Hee | - |
dc.contributor.affiliatedAuthor | Kim, Eun Young | - |
dc.contributor.affiliatedAuthor | Kim, Jinna | - |
dc.contributor.affiliatedAuthor | Kim, Hye Ryun | - |
dc.contributor.affiliatedAuthor | Paik, Soon Myung | - |
dc.contributor.affiliatedAuthor | Shim, Hyo Sup | - |
dc.contributor.affiliatedAuthor | Lee, Jin Gu | - |
dc.contributor.affiliatedAuthor | Cho, Byoung Chul | - |
dc.contributor.affiliatedAuthor | Hong, Min Hee | - |
dc.citation.volume | 28 | - |
dc.citation.number | 6 | - |
dc.citation.startPage | 1250 | - |
dc.citation.endPage | 1259 | - |
dc.identifier.bibliographicCitation | ANNALS OF ONCOLOGY, Vol.28(6) : 1250-1259, 2017 | - |
dc.identifier.rimsid | 51408 | - |
dc.type.rims | ART | - |
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