Department of Medical Oncology and Hematology, Princess Margaret Hospital, University Health Network, University of Toronto, Ontario, Canada.
J Thorac Oncol. 2013 May;8(5):530-42. doi: 10.1097/JTO.0b013e318283d958.
A greater understanding of non-small-cell lung cancer at a molecular level has led to the identification of an increasing number of driver mutations. Extensive research of the KRAS gene as well as specific mutations has established its role in tumorigenesis. Nevertheless, the role of KRAS oncogene in non-small-cell lung cancer remains unclear. Recent studies indicated that mutant KRAS could be predictive of lack of response to chemotherapy, but large pooled analysis failed to confirm this result. The predictive value of KRAS mutation and EGFR-TKI treatment is more ambiguous with some recent evidence suggesting that it may be a negative predictive biomarker. This review provides an overview of RAS biology, assesses the utility of KRAS as a prognostic marker, and evaluates its role as a predictive marker for response to chemotherapy and EGFR-TKIs. In addition, we review some current studies that are targeting the KRAS pathway.
对非小细胞肺癌在分子水平上的更深入了解导致了越来越多的驱动突变的识别。对 KRAS 基因及其特定突变的广泛研究确立了其在肿瘤发生中的作用。然而,KRAS 癌基因在非小细胞肺癌中的作用仍不清楚。最近的研究表明,突变型 KRAS 可能预示着对化疗无反应,但大型汇总分析未能证实这一结果。KRAS 突变和 EGFR-TKI 治疗的预测价值更加模糊,一些最新证据表明它可能是一个负预测生物标志物。这篇综述提供了 RAS 生物学的概述,评估了 KRAS 作为预后标志物的效用,并评估了其作为化疗和 EGFR-TKIs 反应预测标志物的作用。此外,我们还回顾了一些目前针对 KRAS 途径的研究。