Personalized Medicine in Non-Small-Cell Lung Cancer: Is KRAS a Useful Marker in Selecting Patients for Epidermal Growth Factor Receptor-Targeted Therapy?
Personalized Medicine in Non-Small-Cell Lung Cancer: Is KRAS a Useful Marker in Selecting Patients for Epidermal Growth Factor Receptor-Targeted Therapy?
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DOI：
10.1200/jco.2009.27.4365
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发表时间：
2010-11-01
影响因子：
45.3
通讯作者：
Socinski, Mark A.
中科院分区：
文献类型：
--
作者：
Roberts, Patrick J.;Stinchcombe, Thomas E.;Socinski, Mark A.
在转移性结直肠癌患者中，建立了KRAS突变状态在选择抗表皮生长因子（EGFR）单克隆抗体治疗患者中的预测价值。在非小细胞肺癌（NSCLC）患者中，确定KRAS突变状态以预测抗egfr治疗的临床获益的效用尚不清楚。本文将简要介绍Ras生物学，概述非小细胞肺癌中Ras信号的异常，并总结使用KRAS突变状态作为抗egfr治疗的阴性预测生物标志物的临床数据。已经进行了KRAS突变状态作为非小细胞肺癌抗egfr治疗临床获益的负面预测因子的回顾性研究；然而，由于KRAS突变的低流行率和肿瘤样本采集率低，样本量小，限制了这些分析的强度。虽然已经观察到KRAS突变的存在与对EGFR酪氨酸激酶抑制剂（TKIs）缺乏反应之间存在关联，但KRAS突变与EGFR TKI无进展和总生存率之间是否存在关联尚不清楚。与结直肠癌不同，KRAS突变似乎不能识别非小细胞肺癌中不能从抗egfr单克隆抗体中获益的患者。检测KRAS突变状态的未来价值可能是排除EGFR突变或间变性淋巴瘤激酶易位的可能性，或确定NSCLC患者的分子亚群，以追求靶向KRAS途径的药物开发策略。[J]中华临床杂志，28(4):479 - 479。(C) 2010年由美国临床肿瘤学会出版
In patients with metastatic colorectal cancer, the predictive value of KRAS mutational status in the selection of patients for treatment with anti-epidermal growth factor (EGFR) monoclonal antibodies is established. In patients with non-small-cell lung cancer (NSCLC), the utility of determining KRAS mutational status to predict clinical benefit to anti-EGFR therapies remains unclear. This review will provide a brief description of Ras biology, provide an overview of aberrant Ras signaling in NSCLC, and summarize the clinical data for using KRAS mutational status as a negative predictive biomarker to anti-EGFR therapies. Retrospective investigations of KRAS mutational status as a negative predictor of clinical benefit from anti-EGFR therapies in NSCLC have been performed; however, small samples sizes as a result of low prevalence of KRAS mutations and the low rate of tumor sample collection have limited the strength of these analyses. Although an association between the presence of KRAS mutation and lack of response to EGFR tyrosine kinase inhibitors (TKIs) has been observed, it remains unclear whether there is an association between KRAS mutation and EGFR TKI progression-free and overall survival. Unlike colorectal cancer, KRAS mutations do not seem to identify patients who do not benefit from anti-EGFR monoclonal antibodies in NSCLC. The future value of testing for KRAS mutational status may be to exclude the possibility of an EGFR mutation or anaplastic lymphoma kinase translocation or to identify a molecular subset of patients with NSCLC in whom to pursue a drug development strategy that targets the KRAS pathway. J Clin Oncol 28:4769-4777. (C) 2010 by American Society of Clinical Oncology