Cited 22 times in
Dual-targeting of EGFR and Neuropilin-1 attenuates resistance to EGFR-targeted antibody therapy in KRAS-mutant non-small cell lung cancer
DC Field | Value | Language |
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dc.contributor.author | 조병철 | - |
dc.date.accessioned | 2020-02-11T06:04:04Z | - |
dc.date.available | 2020-02-11T06:04:04Z | - |
dc.date.issued | 2019 | - |
dc.identifier.issn | 0304-3835 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/174521 | - |
dc.description.abstract | The therapeutic targeting of oncogenic KRAS mutant-harboring (KRASMUT) non-small cell lung cancer (NSCLC) is an urgent unmet need in cancer therapy. Although NSCLC is often driven by epidermal growth factor receptor (EGFR) overexpression and/or mutations, no EGFR-targeted therapy is clinically available for KRASMUT NSCLC. In this study, we show that integrin β3 expression is associated with the intrinsic resistance of KRASMUT NSCLCs to the anti-EGFR antibody cetuximab. Further analyses identified an integrin β3-mediated ternary complex comprising NRP1-integrin β3-KRASMUT and its downstream signaling of PI3K-Akt and RalB-TBK1 as a primary resistance mechanism of KRASMUT NSCLC to cetuximab treatment. Importantly, we demonstrate that the EGFR/NRP1 dual-targeting bispecific antibody, Ctx-TPP11, attenuates the downstream signaling driven by the ternary complex via the cellular co-internalization and degradation of the NRP1-coupled complex, resulting in the alleviation of cetuximab resistance in KRASMUT NSCLCs in vitro and in vivo, including patient-derived xenograft mouse models. Our study shows that the dual-targeting of EGFR and NRP1 with a bispecific antibody might be an effective therapeutic strategy for KRASMUT NSCLC. | - |
dc.description.statementOfResponsibility | restriction | - |
dc.language | English | - |
dc.publisher | Elsevier Science Ireland | - |
dc.relation.isPartOf | CANCER LETTERS | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.title | Dual-targeting of EGFR and Neuropilin-1 attenuates resistance to EGFR-targeted antibody therapy in KRAS-mutant non-small cell lung cancer | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학교실) | - |
dc.contributor.googleauthor | Ye-Jin Kim | - |
dc.contributor.googleauthor | Du-San Baek | - |
dc.contributor.googleauthor | Seyoung Lee | - |
dc.contributor.googleauthor | Daechan Park | - |
dc.contributor.googleauthor | Han Na Kang | - |
dc.contributor.googleauthor | Byoung Chul Cho | - |
dc.contributor.googleauthor | Yong-Sung Kim | - |
dc.identifier.doi | 10.1016/j.canlet.2019.09.005 | - |
dc.contributor.localId | A03822 | - |
dc.relation.journalcode | J00448 | - |
dc.identifier.eissn | 1872-7980 | - |
dc.identifier.pmid | 31521695 | - |
dc.identifier.url | https://www.sciencedirect.com/science/article/pii/S0304383519304690 | - |
dc.subject.keyword | Bispecific antibody | - |
dc.subject.keyword | Cetuximab resistance | - |
dc.subject.keyword | EGFR/NRP1 dual-targeting | - |
dc.subject.keyword | Integrin β3 | - |
dc.subject.keyword | KRAS mutation | - |
dc.contributor.alternativeName | Cho, Byoung Chul | - |
dc.contributor.affiliatedAuthor | 조병철 | - |
dc.citation.volume | 466 | - |
dc.citation.startPage | 23 | - |
dc.citation.endPage | 34 | - |
dc.identifier.bibliographicCitation | CANCER LETTERS, Vol.466 : 23-34, 2019 | - |
dc.identifier.rimsid | 64339 | - |
dc.type.rims | ART | - |
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