PDF(Pubmed)
Abstract：
BACKGROUND: For several years, the AXL tyrosine kinase receptor, a member of the Tyro3-Axl-Mer (TAM) family, has been considered a new strategic target in oncology. AXL overexpression is common in solid tumors and is associated with poor prognosis. In this context, the detection of a subset of circulating tumor cells (CTCs) that express AXL (AXL+ CTCs) could be clinically relevant.
METHODS: Immunostaining was performed to assess AXL expression in human breast cancer cell lines. The optimal conditions were established using flow cytometry. Spiking experiments were carried out to optimize the parameters of the CellSearch® system detection test. CTC enumeration and AXL expression were evaluated in patients with metastatic breast cancer (mBC) before treatment initiation.
RESULTS: An innovative AXL+ CTC detection assay to be used with the CellSearch® system was developed. In a prospective longitudinal clinical trial, blood samples from 60 patients with untreated mBC were analyzed to detect AXL+ CTCs with this new assay. CTCs were detected in 35/60 patients (58.3%) and AXL+ CTCs were identified in 7 of these 35 patients (11.7% of all patients).
CONCLUSIONS: This newly established AXL+ CTC assay is a promising tool that can be used for liquid biopsy in future clinical trials to stratify and monitor patients with cancer receiving anti-AXL therapies.
METHODS: Immunostaining was performed to assess AXL expression in human breast cancer cell lines. The optimal conditions were established using flow cytometry. Spiking experiments were carried out to optimize the parameters of the CellSearch® system detection test. CTC enumeration and AXL expression were evaluated in patients with metastatic breast cancer (mBC) before treatment initiation.
RESULTS: An innovative AXL+ CTC detection assay to be used with the CellSearch® system was developed. In a prospective longitudinal clinical trial, blood samples from 60 patients with untreated mBC were analyzed to detect AXL+ CTCs with this new assay. CTCs were detected in 35/60 patients (58.3%) and AXL+ CTCs were identified in 7 of these 35 patients (11.7% of all patients).
CONCLUSIONS: This newly established AXL+ CTC assay is a promising tool that can be used for liquid biopsy in future clinical trials to stratify and monitor patients with cancer receiving anti-AXL therapies.
摘要：
背景：几年来，AXL酪氨酸激酶受体，Tyro3-Axl-Mer（TAM）家族的成员，被认为是肿瘤学的新战略目标。AXL过表达在实体瘤中常见且与不良预后相关。在这种情况下，表达AXL(AXL+CTC)的循环肿瘤细胞(CTC)亚群的检测可能与临床相关.
方法:进行免疫染色以评估人乳腺癌细胞系中的AXL表达。使用流式细胞术建立了最佳条件。进行加标实验以优化CellSearch®系统检测测试的参数。在治疗开始前评估转移性乳腺癌（mBC）患者的CTC计数和AXL表达。
结果：开发了一种与CellSearch®系统一起使用的创新的AXL+CTC检测方法。在一项前瞻性纵向临床试验中,我们对60例未经治疗的mBC患者的血样进行了分析,以采用这种新方法检测AXL+CTC.在35/60名患者(58.3%)中检测到CTC,并且在这35名患者中的7名(所有患者的11.7%)中鉴定出AXL+CTC。
结论：这种新建立的AXL+CTC测定法是一种有前途的工具，可用于未来临床试验中的液体活检，以分层和监测接受抗AXL治疗的癌症患者。
方法:进行免疫染色以评估人乳腺癌细胞系中的AXL表达。使用流式细胞术建立了最佳条件。进行加标实验以优化CellSearch®系统检测测试的参数。在治疗开始前评估转移性乳腺癌（mBC）患者的CTC计数和AXL表达。
结果：开发了一种与CellSearch®系统一起使用的创新的AXL+CTC检测方法。在一项前瞻性纵向临床试验中,我们对60例未经治疗的mBC患者的血样进行了分析,以采用这种新方法检测AXL+CTC.在35/60名患者(58.3%)中检测到CTC,并且在这35名患者中的7名(所有患者的11.7%)中鉴定出AXL+CTC。
结论：这种新建立的AXL+CTC测定法是一种有前途的工具，可用于未来临床试验中的液体活检，以分层和监测接受抗AXL治疗的癌症患者。
