Dana-Farber Cancer Institute, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA 02215, USA.
J Clin Oncol. 2013 Mar 10;31(8):1097-104. doi: 10.1200/JCO.2012.42.9829. Epub 2013 Feb 11.
The identification of oncogenic driver mutations underlying sensitivity to epidermal growth factor receptor and anaplastic lymphoma kinase tyrosine kinase inhibitors has led to a surge of interest in identifying additional targetable oncogenes in non-small-cell lung cancer. A number of new potentially oncogenic gene alterations have been characterized in recent years, including BRAF mutations, HER2 insertions, PIK3CA mutations, FGFR1 amplifications, DDR2 mutations, ROS1 rearrangements, and RET rearrangements. In this review, we will discuss the techniques used to discover each of these candidate oncogenes, the prevalence of each in non-small-cell lung cancer, the preclinical data supporting their role in lung cancer, and data on small molecular inhibitors in development.
致癌驱动突变的鉴定，这些突变使非小细胞肺癌对表皮生长因子受体和间变性淋巴瘤激酶酪氨酸激酶抑制剂敏感，这使得人们对鉴定非小细胞肺癌中其他可靶向的致癌基因产生了浓厚的兴趣。近年来，已经鉴定了许多新的潜在致癌基因突变，包括 BRAF 突变、HER2 插入、PIK3CA 突变、FGFR1 扩增、DDR2 突变、ROS1 重排和 RET 重排。在这篇综述中，我们将讨论发现这些候选致癌基因的技术，每种基因在非小细胞肺癌中的发生率，支持其在肺癌中作用的临床前数据，以及正在开发的小分子抑制剂的数据。
