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

Lori J. Goldstein, Raymond P. Perez, Denise Yardley, Linda K. Han, James M. Reuben, Hui Gao, Susan McCanna, Beth Butler, Pier Adelchi Ruffini, Yi Liu, Roberto R. Rosato, Jenny C. Chang

Research output: Contribution to journalArticle

1 Scopus citations

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.

Original languageEnglish (US)
Article number4
JournalBreast Cancer Research
Volume22
Issue number1
DOIs
StatePublished - Jan 10 2020

Keywords

  • Autophagy
  • CXCR1
  • Cancer stem cells
  • Reparixin

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Goldstein, L. J., Perez, R. P., Yardley, D., Han, L. K., Reuben, J. M., Gao, H., McCanna, S., Butler, B., Ruffini, P. A., Liu, Y., Rosato, R. R., & Chang, J. C. (2020). A window-of-opportunity trial of the CXCR1/2 inhibitor reparixin in operable HER-2-negative breast cancer. Breast Cancer Research, 22(1), [4]. https://doi.org/10.1186/s13058-019-1243-8