{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T20:28:28Z","timestamp":1792528108412,"version":"4.5.0"},"reference-count":34,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22K08764"],"award-info":[{"award-number":["22K08764"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["24K11755"],"award-info":[{"award-number":["24K11755"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["25K02712"],"award-info":[{"award-number":["25K02712"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>In breast cancer, elevated serum interleukin\u20106 (IL\u20106) level is associated with a poor prognosis during eribulin treatment; however, the mechanisms underlying IL\u20106\u2010mediated resistance and its potential as a therapeutic target remain unclear. We aimed to determine whether IL\u20106 is involved in eribulin resistance and evaluate the therapeutic potential of combining eribulin with an IL\u20106 receptor\u2010specific inhibitor to overcome resistance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Eribulin\u2010resistant cell lines (MCF\u20107E and MDA\u2010MB\u2010231E) were established through prolonged culture with eribulin. IL\u20106 in conditioned media was quantified using enzyme\u2010linked immunosorbent assay, and RNA\u2010seq was performed to identify pathways associated with eribulin resistance. The therapeutic efficacy of eribulin in combination with tocilizumab (TCZ), an IL\u20106 receptor inhibitor, was assessed using a patient\u2010derived xenograft (PDX) mouse model with acquired eribulin resistance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The IC\n                      <jats:sub>50<\/jats:sub>\n                      of eribulin in both MCF\u20107E and MDA\u2010MB\u2010231E cells was &gt;\u2009500\u2010fold higher than that of their parental counterparts. RNA\u2010seq revealed significant activation of several signaling pathways, particularly the IL\u20106\u2013JAK\u2013STAT pathway, in eribulin\u2010resistant cells but not in doxorubicin\u2010resistant MCF\u20107D cells. Gene set enrichment analysis confirmed the enrichment of IL\u20106\u2013JAK\u2013STAT pathway\u2010related genes in MCF\u20107E and MDA\u2010MB\u2010231E. Although TCZ alone had no effect on cell viability, its combination with eribulin had a synergistic inhibitory effect on MDA\u2010MB\u2010231 cells. In the PDX model, tumor growth in the eribulin\u2009+\u2009TCZ group was significantly suppressed compared with that in the eribulin\u2010only group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings suggest that IL\u20106 contributes to eribulin resistance in breast cancer and that IL\u20106 receptor inhibition is a promising therapeutic strategy to overcome this resistance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.71273","type":"journal-article","created":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T07:41:52Z","timestamp":1762328512000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeting Interleukin\u20106 as a Novel Strategy to Overcome Eribulin Resistance in Breast Cancer"],"prefix":"10.1002","volume":"14","author":[{"given":"Akira","family":"Hattori","sequence":"first","affiliation":[{"name":"Division of Breast and Endocrine Surgery, Department of Surgery Hyogo Medical University  Nishinomiya Hyogo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3462-253X","authenticated-orcid":false,"given":"Masayuki","family":"Nagahashi","sequence":"additional","affiliation":[{"name":"Division of Breast and Endocrine Surgery, Department of Surgery Hyogo Medical University  Nishinomiya Hyogo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miki","family":"Komatsu","sequence":"additional","affiliation":[{"name":"Division of Breast and Endocrine Surgery, Department of Surgery Hyogo Medical University  Nishinomiya Hyogo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayaka","family":"Urano","sequence":"additional","affiliation":[{"name":"Division of Breast and 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