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A window-of-opportunity trial of the CXCR1/2 inhibitor reparixin in operable HER-2-negative breast cancer.
Breast Cancer Research ( IF 6.1 ) Pub Date : 2020-01-10 , DOI: 10.1186/s13058-019-1243-8
Lori J Goldstein 1 , Raymond P Perez 2, 3 , Denise Yardley 4 , Linda K Han 5, 6 , James M Reuben 7 , Hui Gao 7 , Susan McCanna 8 , Beth Butler 8 , Pier Adelchi Ruffini 8 , Yi Liu 9 , Roberto R Rosato 9 , Jenny C Chang 9
Affiliation  

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.

中文翻译:

CXCR1 / 2抑制剂reparixin在可手术的HER-2阴性乳腺癌中的机会窗试验。

背景技术据称癌症干细胞(CSC)负责肿瘤的发生,治疗的抵抗力,疾病的复发和转移。CXCR1是CXCL8的受体之一,已在乳腺癌(BC)CSC上鉴定出来。Reparixin是一种研究性的CXCR1变构抑制剂,可降低小鼠BC异种移植物中CSC的含量。方法在这项多中心,单臂试验中,HER-2阴性可操作性BC的妇女在手术前21天每天3次每天接受1000毫克的瑞帕新口服片剂。主要目标评估了在基线和治疗完成时进行的核心活检中瑞帕新的安全性以及瑞帕新对CSC和肿瘤微环境的影响。活动信号定义为流式细胞术检测ALDH +或CD24- / CD44 + CSC降低≥20%,而免疫组织化学法则一致降低。结果招募了20名患者并完成了研究。没有严重的不良反应。通过流式细胞术测量的CSC标记ALDH +和CD24- / CD44 +在4/17和9/17可评估患者中分别降低了≥20%。但是,由于CSC的数量非常少,因此无法通过免疫荧光法确认这些结果。结论Reparixin看起来安全且耐受良好。通过流式细胞仪检测,几名患者的CSC降低,表明CXCR1靶向CSC。临床试验注册Clinicaltrials.gov,NCT01861054。2013年4月18日注册。由于CSC的数量非常少,因此无法通过免疫荧光法确认这些结果。结论Reparixin看起来安全且耐受良好。通过流式细胞仪检测,几名患者的CSC降低,表明CXCR1靶向CSC。临床试验注册Clinicaltrials.gov,NCT01861054。2013年4月18日注册。由于CSC的数量非常少,因此无法通过免疫荧光法确认这些结果。结论Reparixin看起来安全且耐受良好。通过流式细胞仪检测,几名患者的CSC降低,表明CXCR1靶向CSC。临床试验注册Clinicaltrials.gov,NCT01861054。2013年4月18日注册。
更新日期:2020-04-22
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