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Tumors co-opt many of these fundamental processes to directly stimulate proliferation, invasion, and metastasis of cancer cells. CXCR4 signaling contributes to critical functions of stromal cells in cancer, including angiogenesis and multiple cell types in the tumor immune environment. Studies in animal models of several different types of cancers consistently demonstrate essential functions of CXCR4 in tumor initiation, local invasion, and metastasis to lymph nodes and distant organs. Data from animal models support clinical observations showing that integrated effects of CXCR4 on cancer and stromal cells correlate with metastasis and overall poor prognosis in &amp;gt;20 different human malignancies. Small molecules, Abs, and peptidic agents have shown anticancer efficacy in animal models, sparking ongoing efforts at clinical translation for cancer therapy. Investigators also are developing companion CXCR4-targeted imaging agents with potential to stratify patients for CXCR4-targeted therapy and monitor treatment efficacy. Here, pre-clinical studies demonstrating functions of CXCR4 in cancer are reviewed.<\/jats:p>","DOI":"10.1002\/jlb.2bt1018-715rr","type":"journal-article","created":{"date-parts":[[2020,10,26]],"date-time":"2020-10-26T16:14:01Z","timestamp":1603728841000},"page":"969-989","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["At the Bench: Pre-clinical evidence for multiple functions of CXCR4 in cancer"],"prefix":"10.1093","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6832-2581","authenticated-orcid":true,"given":"Gary D","family":"Luker","sequence":"first","affiliation":[{"name":"Departments of Radiology, Biomedical Engineering, and Microbiology and Immunology, University of Michigan , Ann Arbor, Michigan , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinming","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Medicine, Vanderbilt University , Nashville, Tennessee , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Richmond","sequence":"additional","affiliation":[{"name":"School of Medicine, Vanderbilt University , Nashville, Tennessee , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Scala","sequence":"additional","affiliation":[{"name":"Research Department, Microenvironment Molecular Targets, Istituto Nazionale Tumori IRCCS \u201cFondazione G. Pascale\u201d , Napoli , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Festuccia","sequence":"additional","affiliation":[{"name":"Department of Applied Clinical Science and Biotechnologies, Laboratory of Radiobiology, University of L\u2019Aquila , L\u2019Aquila , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margret","family":"Schottelius","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Centre Hospitalier Universitaire Vaudois, and Department of Oncology, University of Lausanne , Lausanne , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-J\u00fcrgen","family":"Wester","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Technical University of Munich , Garching , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johann","family":"Zimmermann","sequence":"additional","affiliation":[{"name":"Polyphor Ltd , 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