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Although MTAs are not effective for treatment of colorectal cancer (CRC), preclinical studies suggest that a subset of patients with CRC, especially those with cancers harboring the <jats:italic>BRAF<\/jats:italic> mutation, could benefit from such agents. However, two MTAs, eribulin (Eri) and vinorelbine, have shown limited clinical efficacy. Here, we report that insulin\u2010like growth factor 1 receptor (IGF\u20101R) signaling is involved in Eri resistance. Using CRC cell lines, we showed that Eri induces activation and subsequent translocation of IGF\u20101R to the nucleus. When the activation and\/or nuclear translocation of IGF\u20101R was inhibited, Eri induced DNA damage and enhanced G<jats:sub>2<\/jats:sub>\/M arrest. In a xenograft model using the Eri\u2010resistant SW480 cell line, the combination of Eri and the IGF\u20101R inhibitor linsitinib suppressed tumor growth more efficiently than either single agent. Thus, our results indicated that combination dosing with Eri and an IGF\u20101R inhibitor could overcome Eri resistance and offer a therapeutic opportunity in CRC.<\/jats:p>","DOI":"10.1111\/cas.15558","type":"journal-article","created":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T13:34:52Z","timestamp":1662125692000},"page":"4207-4218","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Inhibition of insulin\u2010like growth factor\u20101 receptor enhances eribulin\u2010induced <scp>DNA<\/scp> damage in colorectal cancer"],"prefix":"10.1111","volume":"113","author":[{"given":"Tomoyasu","family":"Yoshihiro","sequence":"first","affiliation":[{"name":"Department of Medicine and Biosystemic Science Kyushu University Graduate School of Medical Sciences  Fukuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8374-5045","authenticated-orcid":false,"given":"Hiroshi","family":"Ariyama","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Cardiovascular Medicine Kyushu University Hospital  Fukuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyoko","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Cardiovascular Medicine Kyushu University Hospital  Fukuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Imajima","sequence":"additional","affiliation":[{"name":"Department of Medicine and Biosystemic Science Kyushu University Graduate School of Medical Sciences  Fukuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoru","family":"Yamaga","sequence":"additional","affiliation":[{"name":"Department of Medicine and Biosystemic Science Kyushu University Graduate School of Medical Sciences  Fukuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenji","family":"Tsuchihashi","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Cardiovascular Medicine Kyushu University Hospital  Fukuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5686-1940","authenticated-orcid":false,"given":"Taichi","family":"Isobe","sequence":"additional","affiliation":[{"name":"Department of Oncology and Social Medicine, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hitoshi","family":"Kusaba","sequence":"additional","affiliation":[{"name":"Department of Medicine and Biosystemic Science Kyushu University Graduate School of Medical Sciences  Fukuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koichi","family":"Akashi","sequence":"additional","affiliation":[{"name":"Department of Medicine and Biosystemic Science Kyushu University Graduate School of Medical Sciences  Fukuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9428-6772","authenticated-orcid":false,"given":"Eishi","family":"Baba","sequence":"additional","affiliation":[{"name":"Department of Oncology and Social Medicine, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,9,13]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"WHO cancer today(2018). 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