{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T12:21:31Z","timestamp":1784636491501,"version":"3.55.0"},"reference-count":58,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,2,9]],"date-time":"2025-02-09T00:00:00Z","timestamp":1739059200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002701","name":"Ministry of Education","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002701","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Papillary thyroid cancer (PTC) is a general thyroid cancer subtype; however, PTC is associated with metastasis or recurrence via anti\u2010cancer drug resistance, rendering it practically incurable. Therefore, effective and reliable clinical approaches are urgently required.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>We demonstrated the coordinated up\u2010regulation of sarco\/endoplasmic reticulum (ER) calcium ATPase 1 (SERCA1) in metastatic PTC under treatment with sorafenib or lenvatinib. We screened novel drug candidates in a patient\u2010derived lymph node metastatic PTC and compared outcomes with those in non\u2010metastatic and main mass PTC in an in vitro and in vivo model to propose a new clinical strategy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>In the current study using patient\u2010derived metastatic PTC cells, SERCA1 was considerably increased under sorafenib\u2010 or lenvatinib\u2010treated conditions. SERCA is a critical component in cytosolic free calcium regulation and is regulated by calcium\/calmodulin\u2010dependent protein kinase 2 alpha (CaMK2\u03b1) via NF\u03baB. However, cardiac dysfunction was inevitable in vivo because of non\u2010specific inhibition of SERCA isoforms by conventional SERCA inhibitors. This study designed a therapeutic approach with decreased cardiac dysfunction via SERCA1 isoform\u2013specific inhibition by novel small molecules, CKP1 and CKP2, under severe ER stress conditions in patient\u2010derived metastatic PTC. These novel SERCA1\u2010specific inhibitors remarkably increased tumour shrinkage in the patient\u2010derived metastatic PTC xenograft tumour model without cardiac dysfunction when used in combination with sorafenib or lenvatinib.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>These outcomes suggest the potential efficacy of the novel combination strategy that uses targeted therapy to treat malignant cancer cells, such as sorafenib\u2010 or lenvatinib\u2010resistant cancer cells.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.17442","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T08:42:15Z","timestamp":1739263335000},"page":"2392-2408","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Identification of new small molecules for selective inhibition of SERCA 1 in patient\u2010derived metastatic papillary thyroid cancer"],"prefix":"10.1111","volume":"182","author":[{"given":"Seok\u2010Mo","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Surgery, Thyroid Cancer Center, Gangnam Severance Hospital, Institute of Refractory Thyroid Cancer Yonsei University College of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keunwan","family":"Park","sequence":"additional","affiliation":[{"name":"Natural Product Informatics Research Center KIST Gangneung Institute of Natural Products  Gangneung South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeok Jun","family":"Yun","sequence":"additional","affiliation":[{"name":"Department of Surgery, Thyroid Cancer Center, Gangnam Severance Hospital, Institute of Refractory Thyroid Cancer Yonsei University College of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung 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