一种用于监测抗 EGFR 治疗反应的血液生物标志物。

A blood biomarker for monitoring response to anti-EGFR therapy.

机构信息

Molecular Imaging Program at Stanford, Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.

Canary Center at Stanford for Cancer Early Detection, Palo Alto, CA, USA.

出版信息

Cancer Biomark. 2018;22(2):333-344. doi: 10.3233/CBM-171149.

DOI:10.3233/CBM-171149

PMID:29689709

Abstract

BACKGROUND AND OBJECTIVE

To monitor therapies targeted to epidermal growth factor receptors (EGFR) in non-small cell lung cancer (NSCLC), we investigated Peroxiredoxin 6 (PRDX6) as a biomarker of response to anti-EGFR agents.

METHODS

We studied cells that are sensitive (H3255, HCC827) or resistant (H1975, H460) to gefitinib. PRDX6 was examined with either gefitinib or vehicle treatment using enzyme-linked immunosorbent assays. We created xenograft models from one sensitive (HCC827) and one resistant cell line (H1975) and monitored serum PRDX6 levels during treatment.

RESULTS

PRDX6 levels in cell media from sensitive cell lines increased significantly after gefitinib treatment vs. vehicle, whereas there was no significant difference for resistant lines. PRDX6 accumulation over time correlated positively with gefitinib sensitivity. Serum PRDX6 levels in gefitinib-sensitive xenograft models increased markedly during the first 24 hours of treatment and then decreased dramatically during the following 48 hours. Differences in serum PRDX6 levels between vehicle and gefitinib-treated animals could not be explained by differences in tumor burden.

CONCLUSIONS

Our results show that changes in serum PRDX6 during the course of gefitinib treatment of xenograft models provide insight into tumor response and such an approach offers several advantages over imaging-based strategies for monitoring response to anti-EGFR agents.

摘要

背景与目的

为了监测表皮生长因子受体（EGFR）靶向疗法在非小细胞肺癌（NSCLC）中的应用，我们研究了过氧化物酶 6（PRDX6）作为抗 EGFR 药物反应的生物标志物。

方法

我们研究了对吉非替尼敏感（H3255、HCC827）或耐药（H1975、H460）的细胞。使用酶联免疫吸附试验（ELISA）分别用吉非替尼或载体处理细胞，检测 PRDX6。我们从一个敏感（HCC827）和一个耐药细胞系（H1975）中建立了异种移植模型，并在治疗过程中监测血清 PRDX6 水平。

结果

与载体处理相比，敏感细胞系的细胞培养基中的 PRDX6 水平在吉非替尼处理后显著增加，而耐药细胞系则没有显著差异。PRDX6 的积累随时间与吉非替尼敏感性呈正相关。吉非替尼敏感的异种移植模型中，血清 PRDX6 水平在治疗的前 24 小时内显著增加，然后在接下来的 48 小时内急剧下降。与载体相比，在接受吉非替尼治疗的动物中，血清 PRDX6 水平的差异不能用肿瘤负荷的差异来解释。