Lee Jeeyun, Ou Sai-Hong Ignatius
Department of Hematology and Oncology, Samsung Medical Center, SungKyunKwan University School of Medicine, Seoul, 135-710, South Korea.
Discov Med. 2013 Jun;15(85):333-41.
Gastric cancer is the second leading cancer cause of death globally. Apart from the successful targeting of HER2 over-expression in gastric cancer (GC) with trastuzumab, other targeted therapies in GC have fallen short or still in early clinical development. While HER2 over-expression accounts for up to 20% of GC, other potential actionable driver mutations occur a much lower frequency in GC. In this review we describe some of the more interesting genetic aberrations including driver mutations in gastric cancer that have very potent inhibitors against them already in clinical development. Part I of this review will focus on the receptor tyrosine kinase (RTK) gene amplification (HER2, FGFR2, MET, EGFR). Part II will devoted to gene mutations (HER2, KRAS, PIK3CA, BRAF) and gene rearrangement (ROS1, BRAF, HER2). Because of the low frequency of these potential driver mutations, perseverance in screening for these mutations will be needed in order to enroll enough of each uniquely molecularly defined subset of GC in order to demonstrate significant clinical benefit in a unique molecularly targeted therapy trial. This approach has been successfully employed in the clinical approval of crizotinib for the treatment of ALK-rearranged non-small cell lung cancer.
胃癌是全球第二大致死性癌症。除了用曲妥珠单抗成功靶向治疗胃癌（GC）中HER2过表达外，GC中的其他靶向治疗要么效果不佳，要么仍处于临床早期开发阶段。虽然HER2过表达在GC中占比高达20%，但其他潜在的可操作驱动突变在GC中的发生频率要低得多。在本综述中，我们描述了一些更有趣的基因畸变，包括胃癌中的驱动突变，针对这些突变已有非常有效的抑制剂正在临床开发中。本综述的第一部分将聚焦于受体酪氨酸激酶（RTK）基因扩增（HER2、FGFR2、MET、EGFR）。第二部分将致力于基因突变（HER2、KRAS、PIK3CA、BRAF）和基因重排（ROS1、BRAF、HER2）。由于这些潜在驱动突变的频率较低，需要坚持筛查这些突变，以便招募足够数量的GC各独特分子定义亚组患者，从而在独特的分子靶向治疗试验中证明显著的临床获益。这种方法已成功用于克唑替尼治疗ALK重排非小细胞肺癌的临床批准。
