{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T04:03:02Z","timestamp":1790222582108,"version":"4.1.0"},"reference-count":75,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,12,20]],"date-time":"2019-12-20T00:00:00Z","timestamp":1576800000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Metastatic castration resistant prostate cancer (mCRPC) relapses due to acquired resistance to docetaxel-based chemotherapy and remains a major threat to patient survival. In this report, we tested the effectiveness of a dual CXCR4\/E-selectin antagonist, GM-I1359, in vitro and in vivo, as a single agent or in combination with docetaxel (DTX). This agent was compared to the single CXCR4 antagonist, CTCE-9908, and E-selectin antagonist, GMI-1271. Here we demonstrate that CXCR4 antagonism reduced growth and enhanced DTX treatment in PCa cell lines as well as restored DTX effectiveness in DTX-resistant cell models. The efficacy of dual antagonist was higher respect to those observed for single CXCR4 antagonism. GM1359 impacted bone marrow colonization and growth in intraventricular and intratibial cell injection models. The anti-proliferative effects of GMI-1359 and DTX correlated with decreased size, osteolysis and serum levels of both mTRAP and type I collagen fragment (CTX) in intra-osseous tumours suggesting that the dual CXCR4\/E-selectin antagonist was a docetaxel-sensitizing agent for bone metastatic growth. Single agent CXCR4 (CTCE-9908) and E-selectin (GMI-1271) antagonists resulted in lower sensitizing effects compared to GMI-1359. These data provide a biologic rationale for the use of a dual E-selectin\/CXCR4 inhibitor as an adjuvant to taxane-based chemotherapy in men with mCRPC to prevent and reduce bone metastases.<\/jats:p>","DOI":"10.3390\/cells9010032","type":"journal-article","created":{"date-parts":[[2019,12,23]],"date-time":"2019-12-23T03:23:12Z","timestamp":1577071392000},"page":"32","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Dual CXCR4 and E-Selectin Inhibitor, GMI-1359, Shows Anti-Bone Metastatic Effects and Synergizes with Docetaxel in Prostate Cancer Cell Intraosseous Growth"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3463-6475","authenticated-orcid":false,"given":"Claudio","family":"Festuccia","sequence":"first","affiliation":[{"name":"Department of Biotechnological and Applied Clinical Sciences, Laboratory of Radiobiology, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Mancini","sequence":"additional","affiliation":[{"name":"Department of Biotechnological and Applied Clinical Sciences, Laboratory of Radiobiology, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"},{"name":"Multi-Factorial Disease and Complex Phenotype Research Area, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Viale di San Paolo 15, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni Luca","family":"Gravina","sequence":"additional","affiliation":[{"name":"Department of Biotechnological and Applied Clinical Sciences, Laboratory of Radiobiology, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"},{"name":"Department of Biotechnological and Applied Clinical Sciences, Division of Radiation Oncology, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Colapietro","sequence":"additional","affiliation":[{"name":"Department of Biotechnological and Applied Clinical Sciences, Laboratory of Radiobiology, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Vetuschi","sequence":"additional","affiliation":[{"name":"Department of Biotechnological and Applied Clinical Sciences, Laboratory of Human Anatomy, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Pompili","sequence":"additional","affiliation":[{"name":"Department of Biotechnological and Applied Clinical Sciences, Laboratory of Human Anatomy, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Ventura","sequence":"additional","affiliation":[{"name":"Pathology Department, San Salvatore Hospital, 67100 L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8153-915X","authenticated-orcid":false,"given":"Simona","family":"Delle Monache","sequence":"additional","affiliation":[{"name":"Department of Biotechnological and Applied Clinical Sciences, Laboratory of Applied Biology, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1863-5752","authenticated-orcid":false,"given":"Roberto","family":"Iorio","sequence":"additional","affiliation":[{"name":"Department of Life, Health and Environmental Sciences, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Del Fattore","sequence":"additional","affiliation":[{"name":"Multi-Factorial Disease and Complex Phenotype Research Area, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Viale di San Paolo 15, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Fogler","sequence":"additional","affiliation":[{"name":"GlycoMimetics Inc., Gaithersburg, MD 20850, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Magnani","sequence":"additional","affiliation":[{"name":"GlycoMimetics Inc., Gaithersburg, MD 20850, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1093\/annonc\/mdw027","article-title":"The global decrease in cancer mortality: Trends and disparities","volume":"27","author":"Hashim","year":"2016","journal-title":"Ann. 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