Clinical development of QUEEN assay, a novel biomarker for predicting the sensitivity of non small cell lung cancer to epidermal growth factor receptor inhibitors

表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)对部分晚期非小细胞肺癌(NSCLC)患者具有良好的抗肿瘤活性。通过基因芯片分析，我们先前发现了12个吉非替尼耐药相关基因在EGFR-TKI应答者和无应答者之间差异表达(S Kakiuchi等，Hum Mol Genet)。2004年)。我们开发了一个有用的吉非替尼疗效预测系统，通过使用定量RT-PCR来测量这些基因的表达水平。该系统评估的预测评分与接受吉非替尼治疗的晚期非小细胞肺癌患者的疗效、进展时间和生存期密切相关。然而，厄洛替尼是一种新型的EGFR-TKI，于2008年获得批准，并已被用作先前治疗的非小细胞肺癌患者的标准治疗方案。在本研究中，我们在治疗开始前用该系统评估非小细胞肺癌对厄洛替尼的敏感性，以证实该预测系统的准确性和有效性。虽然这项研究尚未完成，但对最佳总体反应的预测准确率达到85.7%(12/14)，提示该系统可能成为EGR-TKI治疗的一个临床有用的预测指标。

Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), has shown a favorable anti-tumor activity to a subset of patients with advanced non-small-cell lung cancer (NSCLC). By DNA microarray analyses, we previously identified twelve gefitinib-resistance related genes differentially expressed between responders and non-responders to EGFR-TKI (S kakiuchi, et al, Hum Mol Genet. 2004). We developed a useful gefitinib-efficacy prediction system by measuring the expression levels of these genes using quantitative RT-PCR. The prediction score assessed by this system closely correlated with the outcome of the patients with advanced NSCLC treated with gefitinib, in terms of the responses, time to progression, and survival duration. However, erlotinib, a novel EGFR-TKI, has approved in 2008, and has been used as a standard therapy for the previous treated NSCLC patients. In this study, we evaluated the sensitivity of NSCLC to erlotinib by this system before the initiation of the treatment, in order to confirm the accuracy and efficacy of this prediction system. Although this study has not finished yet, the accuracy is reached to 85.7%(12/14) on prediction of best overall response, suggesting that this system may be a clinical useful predictive marker for EGR-TKI treatment.