Hyperactivation of TORC1 Drives Resistance to the Pan-HER Tyrosine Kinase Inhibitor Neratinib in HER2-Mutant Cancers
DC Field | Value | Language |
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dc.contributor.author | Sudhan, Dhivya R. | - |
dc.contributor.author | Guerrero-Zotano, Angel | - |
dc.contributor.author | Won, Helen | - |
dc.contributor.author | Ericsson, Paula Gonzalez | - |
dc.contributor.author | Servetto, Alberto | - |
dc.contributor.author | Huerta-Rosario, Mariela | - |
dc.contributor.author | Ye, Dan | - |
dc.contributor.author | Lee, Kyung min | - |
dc.contributor.author | Formisano, Luigi | - |
dc.contributor.author | Guo, Yan | - |
dc.contributor.author | Liu, Qi | - |
dc.contributor.author | Kinch, Lisa N. | - |
dc.contributor.author | Brewer, Monica Red | - |
dc.contributor.author | Dugger, Teresa | - |
dc.contributor.author | Koch, James | - |
dc.contributor.author | Wick, Michael J. | - |
dc.contributor.author | Cutler, Richard E., Jr. | - |
dc.contributor.author | Lalani, Alshad S. | - |
dc.contributor.author | Bryce, Richard | - |
dc.contributor.author | Auerbach, Alan | - |
dc.contributor.author | Hanker, Ariella B. | - |
dc.contributor.author | Arteaga, Carlos L. | - |
dc.date.accessioned | 2022-07-08T14:03:13Z | - |
dc.date.available | 2022-07-08T14:03:13Z | - |
dc.date.created | 2021-05-14 | - |
dc.date.issued | 2020-02 | - |
dc.identifier.issn | 1535-6108 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/146163 | - |
dc.description.abstract | We developed neratinib-resistant HER2-mutant cancer cells by gradual dose escalation. RNA sequencing identified TORC1 signaling as an actionable mechanism of drug resistance. Primary and acquired neratinib resistance in HER2-mutant breast cancer patient-derived xenografts (PDXs) was also associated with TORC1 hyperactivity. Genetic suppression of RAPTOR or RHEB ablated P-S6 and restored sensitivity to the tyrosine kinase inhibitor. The combination of the TORC1 inhibitor everolimus and neratinib potently arrested the growth of neratinib-resistant xenografts and organoids established from neratinib-resistant PDXs. RNA and whole-exome sequencing revealed RAS-mediated TORC1 activation in a subset of neratinib-resistant models. DNA sequencing of HER2-mutant tumors clinically refractory to neratinib, as well as circulating tumor DNA profiling of patients who progressed on neratinib, showed enrichment of genomic alterations that converge to activate the mTOR pathway. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | CELL PRESS | - |
dc.title | Hyperactivation of TORC1 Drives Resistance to the Pan-HER Tyrosine Kinase Inhibitor Neratinib in HER2-Mutant Cancers | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Lee, Kyung min | - |
dc.identifier.doi | 10.1016/j.ccell.2019.12.013 | - |
dc.identifier.scopusid | 2-s2.0-85078864506 | - |
dc.identifier.wosid | 000513775300009 | - |
dc.identifier.bibliographicCitation | CANCER CELL, v.37, no.2, pp.183 - 199 | - |
dc.relation.isPartOf | CANCER CELL | - |
dc.citation.title | CANCER CELL | - |
dc.citation.volume | 37 | - |
dc.citation.number | 2 | - |
dc.citation.startPage | 183 | - |
dc.citation.endPage | 199 | - |
dc.type.rims | ART | - |
dc.type.docType | 정기학술지(Article(Perspective Article포함)) | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Oncology | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.relation.journalWebOfScienceCategory | Oncology | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.subject.keywordPlus | PHOSPHOINOSITIDE 3-KINASE P110-ALPHA | - |
dc.subject.keywordPlus | GROWTH-FACTOR RECEPTOR | - |
dc.subject.keywordPlus | ACQUIRED-RESISTANCE | - |
dc.subject.keywordPlus | LUNG CANCERS | - |
dc.subject.keywordPlus | MUTATIONS | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | PI3K-ALPHA | - |
dc.subject.keywordPlus | GENE | - |
dc.subject.keywordPlus | RAS | - |
dc.subject.keywordPlus | TUMORIGENESIS | - |
dc.subject.keywordAuthor | drug resistance | - |
dc.subject.keywordAuthor | HER2 mutations | - |
dc.subject.keywordAuthor | neratinib | - |
dc.subject.keywordAuthor | precision oncology | - |
dc.subject.keywordAuthor | TORC1 | - |
dc.identifier.url | https://www.sciencedirect.com/science/article/pii/S1535610819305835?via%3Dihub | - |
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