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）对晚期非小细胞肺癌（NSCLC）患者具有良好的抗肿瘤活性。通过DNA微阵列分析，我们先前确定了12个吉非替尼耐药相关基因在EGFR-TKI应答者和非应答者之间的差异表达（S kakiuchi等人，Hum Mol Genet. 2004）。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测量这些基因的表达水平。该系统评估的预测评分与吉非替尼治疗晚期NSCLC患者的疗效、进展时间和生存时间密切相关。然而，erlotinib是一种新型EGFR-TKI，已于2008年获批，并已被用作先前治疗过的NSCLC患者的标准治疗。在本研究中，我们在开始治疗前通过该系统评估NSCLC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。虽然本研究尚未结束，但预测最佳总体反应的准确率达到85.7%(12/14)，提示该系统可能是临床有用的EGR-TKI治疗预测指标。

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.