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This is crucial for the development of metastasis in various malignancies, including breast cancer (BC). We previously reported that the loss of FBXW7 in bone marrow\u2010derived stromal cells promoted cancer metastasis by increasing the production of the chemokine CCL2, which attracts myeloid\u2010derived suppressor cells and macrophages to the premetastatic niche. Furthermore, treatment with the CCL2 inhibitor propagermanium (PG), which has been used in Japan as a therapeutic agent against chronic hepatitis B, was shown to block the enhancement of metastasis in FBXW7\u2010deficient mice through inhibiting the formation of premetastatic niches. Here, we describe a phase I dose\u2010escalation study of PG used as an antimetastatic drug for perioperative patients with primary BC. The primary end\u2010point was the percentage of patients who experience dose\u2010limiting toxicity. Twelve patients were enrolled in the study. Dose\u2010limiting toxicity was not observed, and the maximum dose was determined to be 90\u00a0mg\/body\/day. The serum concentrations of PG were nearly within the normal range in all observation days. We observed an inverse correlation between <jats:italic>FBXW7<\/jats:italic> mRNA levels in blood and the serum concentrations of CCL2 and interleukin (IL)\u20106, in agreement with our previous mouse model. Also, IL\u20106 was downregulated in a PG dose\u2010dependent manner, as observed in mice. Thus, PG was given safely and it is expected to have antimetastatic potential in BC. This trial is registered in the UMIN Clinical Trials Registry as UMIN000022494.<\/jats:p>","DOI":"10.1111\/cas.14306","type":"journal-article","created":{"date-parts":[[2020,1,14]],"date-time":"2020-01-14T16:27:29Z","timestamp":1579019249000},"page":"924-931","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Phase I dose\u2010escalation trial to repurpose propagermanium, an oral CCL2 inhibitor, in patients with breast cancer"],"prefix":"10.1111","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6341-2438","authenticated-orcid":false,"given":"Takaaki","family":"Masuda","sequence":"first","affiliation":[{"name":"Department of Surgery Kyushu University Beppu Hospital Beppu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miwa","family":"Noda","sequence":"additional","affiliation":[{"name":"Department of Surgery Kyushu University Beppu Hospital Beppu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Kogawa","sequence":"additional","affiliation":[{"name":"Department of Breast and Medical Oncology National Cancer Center Hospital East Kashiwa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dai","family":"Kitagawa","sequence":"additional","affiliation":[{"name":"Breast Oncology Center The Cancer Institute Hospital Ariake of the Japanese Foundation for Cancer Research Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Department of Surgery Kyushu University Beppu Hospital Beppu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahito","family":"Jomori","sequence":"additional","affiliation":[{"name":"Sanwa Kagaku Kenkyusho Co., Ltd. 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