A window-of-opportunity trial of the CXCR1/2 inhibitor reparixin in operable HER-2-negative breast cancer

Breast Cancer Research

James M. Reuben¹  Hui Gao¹  Lori J. Goldstein²  Linda K. Han³  Pier Adelchi Ruffini⁴  Beth Butler⁴  Susan McCanna⁴  Denise Yardley⁵  Yi Liu⁶  Jenny C. Chang⁶  Roberto R. Rosato⁶  Raymond P. Perez⁷ 

[1]Department of Hematopathology–Research, MD Anderson Cancer Center

[2]Department of Medical Oncology, The Hospital of Fox Chase Cancer Center

[3]Indiana University Simon Cancer Center

[4]Research and Development, Dompé farmaceutici S.p.A.

[5]Tennessee Oncology

[6]The Methodist Hospital Research Institute

[7]University of Kansas Medical Research Center

关键词: Cancer stem cells;    CXCR1;    Reparixin;    Autophagy;   

DOI  :  10.1186/s13058-019-1243-8

来源: DOAJ

【 摘 要 】

Abstract Background Cancer stem cells (CSCs) are purported to be responsible for tumor initiation, treatment resistance, disease recurrence, and metastasis. CXCR1, one of the receptors for CXCL8, was identified on breast cancer (BC) CSCs. Reparixin, an investigational allosteric inhibitor of CXCR1, reduced the CSC content of human BC xenograft in mice. Methods In this multicenter, single-arm trial, women with HER-2-negative operable BC received reparixin oral tablets 1000 mg three times daily for 21 days before surgery. Primary objectives evaluated the safety of reparixin and the effects of reparixin on CSC and tumor microenvironment in core biopsies taken at baseline and at treatment completion. Signal of activity was defined as a reduction of ≥ 20% in ALDH+ or CD24−/CD44+ CSC by flow cytometry, with consistent reduction by immunohistochemistry. Results Twenty patients were enrolled and completed the study. There were no serious adverse reactions. CSC markers ALDH+ and CD24−/CD44+ measured by flow cytometry decreased by ≥ 20% in 4/17 and 9/17 evaluable patients, respectively. However, these results could not be confirmed by immunofluorescence due to the very low number of CSC. Conclusions Reparixin appeared safe and well-tolerated. CSCs were reduced in several patients as measured by flow cytometry, suggesting targeting of CXCR1 on CSC. Clinical trial registration Clinicaltrials.gov, NCT01861054. Registered on April 18, 2013.

【 授权许可】

Unknown