{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T21:44:03Z","timestamp":1788385443716,"version":"build-2803163510"},"reference-count":45,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T00:00:00Z","timestamp":1656288000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["xzy012019078"],"award-info":[{"award-number":["xzy012019078"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81773772"],"award-info":[{"award-number":["81773772"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017596","name":"Natural Science Basic Research Program of Shaanxi Province","doi-asserted-by":"publisher","award":["2022JM\u2010574"],"award-info":[{"award-number":["2022JM\u2010574"]}],"id":[{"id":"10.13039\/501100017596","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Oncology"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:p>\n                    The oncogenic role of ephrin type\u2010B receptor 4 (EPHB4) has been reported in many types of tumors, including chronic myeloid leukemia (CML). Here, we found that CML patients have a higher\n                    <jats:italic>EPHB4<\/jats:italic>\n                    expression level than healthy subjects.\n                    <jats:italic>EPHB4<\/jats:italic>\n                    knockdown inhibited growth of K562 cells (a human immortalized myelogenous leukemia cell line). In addition, transient transfection of\n                    <jats:italic>EPHB4<\/jats:italic>\n                    siRNA led to sensitization to imatinib. These growth defects could be fully rescued by\n                    <jats:italic>EPHB4<\/jats:italic>\n                    transfection. To identify an EPHB4\u2010specific inhibitor with the potential of rapid translation into the clinic, a pool of clinical compounds was screened and vandetanib was found to be most sensitive to K562 cells, which express a high level of EPHB4. Vandetanib mainly acts on the intracellular tyrosine kinase domain and interacts stably with a hydrophobic pocket. Furthermore, vandetanib downregulated EPHB4 protein via the ubiquitin\u2010proteasome pathway and inhibited PI3K\/AKT and MAPK\/ERK signaling pathways in K562 cells. Vandetanib alone significantly inhibited tumor growth in a K562 xenograft model. Furthermore, the combination of vandetanib and imatinib exhibited enhanced and synergistic growth inhibition against imatinib\u2010resistant K562 cells\n                    <jats:italic>in\u2009vitro<\/jats:italic>\n                    and\n                    <jats:italic>in\u2009vivo<\/jats:italic>\n                    . These findings suggest that vandetanib drives growth arrest and overcomes the resistance to imatinib in CML via targeting EPHB4.\n                  <\/jats:p>","DOI":"10.1002\/1878-0261.13270","type":"journal-article","created":{"date-parts":[[2022,6,11]],"date-time":"2022-06-11T02:58:59Z","timestamp":1654916339000},"page":"2747-2765","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Vandetanib drives growth arrest and promotes sensitivity to imatinib in chronic myeloid leukemia by targeting ephrin\n                    <scp>type\u2010B<\/scp>\n                    receptor 4"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6077-904X","authenticated-orcid":false,"given":"Weina","family":"Ma","sequence":"first","affiliation":[{"name":"School of Pharmacy, Health Science Center Xi'an Jiaotong University  China"},{"name":"State Key Laboratory of Shaanxi for Natural Medicines Research 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