CD133+ circulating haematopoietic progenitor cells predict for response to sorafenib plus erlotinib in non-small cell lung cancer patients.
CD133+ circulating haematopoietic progenitor cells predict for response to sorafenib plus erlotinib in non-small cell lung cancer patients.
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DOI：
10.1038/sj.bjc.6605477
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发表时间：
2010-01-19
影响因子：
8.8
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基于血液的生物标志物对于患者选择和预测血管生成抑制剂的治疗反应可能特别有用。循环内皮细胞（CEC）和造血祖细胞（HPC）可能在肿瘤血管生成和肿瘤生长中发挥作用。测量患者血液中的 CEC 和 HPC 可能是监测或预测治疗反应的一种简单、无创的方法。在索拉非尼加厄洛替尼 (SO/ER) 治疗前和治疗期间，测量了 25 名非小细胞肺癌 (NSCLC) 患者血液中的 (VEGFR2+) CEC、(CD133+) HPC、血浆血管内皮生长因子 (VEGF) 和促红细胞生成素。为了评估 CEC 和 HPC 变化的药物特异性，对 18 名接受贝伐单抗加厄洛替尼 (BV/ER) 治疗的患者和 10 名接受厄洛替尼 (ER) 单药治疗的患者进行了研究。根据实体瘤疗效评估标准 (RECIST) 测量所有患者组的疗效。在第7天，与BV/ER治疗的患者（P<0.01）相比，SO/ER治疗的患者的CEC增加了三倍（P<0.0001），并且CEC在厄洛替尼治疗后没有变化（P=0.8）。第 7 天时，SO/ER 治疗后 CD133+/HPC 减少（P<0.0001）。 BV/ER 或厄洛替尼的 HPC 数字均未发生变化。在接受 SO/ER 治疗的患者中，治疗前 CD133+/HPC 在应答者中显着较低 (P=0.01)，并且治疗前 CD133+/HPC 数量低于与较长的进展时间 (TTP) 相关的中位数 (P=0.037)。治疗前 CD133+/HPC 是一种有前途的候选生物标志物，可进一步探索用于选择可能受益于 SO/ER 治疗的 NSCLC 患者。
Blood-based biomarkers may be particularly useful for patient selection and prediction of treatment response for angiogenesis inhibitors. Circulating endothelial cells (CECs) and haematopoietic progenitor cells (HPCs) might have a role in tumour angiogenesis and in tumour growth. Measurement of CECs and HPCs in the blood of patients could be a simple, non-invasive way to monitor or predict responses to treatment. (VEGFR2+) CECs, (CD133+) HPCs, plasma vascular endothelial growth factor (VEGF) and erythropoietin were measured in blood from 25 non-small cell lung cancer (NSCLC) patients before and during treatment with sorafenib plus erlotinib (SO/ER). In order to assess the drug specificity of changes in CECs and HPCs, 18 patients treated with bevacizumab plus erlotinib (BV/ER) and 10 patients with erlotinib (ER) monotherapy were studied. Response was measured in all patient groups by Response Evaluation Criteria in Solid Tumors (RECIST). At day 7, SO/ER-treated patients showed a three-fold increase in CECs (P<0.0001) comparable to BV/ER-treated patients (P<0.01), and the CECs did not change with erlotinib treatment (P=0.8). At day 7, CD133+/HPCs decreased with SO/ER treatment (P<0.0001). HPC numbers did not change with either BV/ER or erlotinib. In SO/ER-treated patients pre-treatment CD133+/HPCs were significantly lower in responders (P=0.01) and pre-treatment CD133+/HPC numbers lower than the median correlated with a longer time-to-progression (TTP) (P=0.037). Pre-treatment CD133+/HPCs are a promising candidate biomarker to further explore for use in selecting NSCLC patients who might benefit from SO/ER treatment.