Novel Targeted Therapies for Esophagogastric Cancer.
Novel Targeted Therapies for Esophagogastric Cancer.
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DOI：
10.1016/j.soc.2016.10.002
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发表时间：
2017-04
影响因子：
1.9
通讯作者：
Catenacci DV
中科院分区：
文献类型：
--
作者：
Maron SB;Catenacci DV
胃食管癌（GEC）仍然是全世界癌症相关死亡的主要原因。尽管美国远端胃腺癌（GC）的发病率正在下降，但近端食管胃结合部腺癌（EGJ）的发病率却在上升。 GEC，包括 GC 和 EGJ，目前在转移环境中采用相同的全身方案进行治疗。转移性疾病的总体生存率仍然很差，迄今为止，很少有分子靶向方法成功纳入常规护理——只有用于 ERBB2 扩增的一线抗 HER2 疗法和二线抗 VEGFR2 疗法成功改善了预后。 GEC 的分子特征鉴定了 EGFR、FGFR2、MET、PI3K 和其他癌基因、候选生物标志物和免疫肿瘤检查点中其他相对频繁的突变和拷贝数变异，这些都可以作为可行的治疗靶点。在这里，我们回顾了这些关键的畸变、它们对蛋白质表达的影响、治疗意义以及每个途径中未来潜在的临床方向。
Gastroesophageal cancer (GEC) remains a major cause of cancer-related mortality worldwide. Although the incidence of distal gastric adenocarcinoma (GC) is declining in the United States, proximal esophagogastric junction adenocarcinoma (EGJ) is rising in incidence. GEC, including GC and EGJ, is currently are treated with the same systemic regimens in the metastatic setting. Overall survival metastatic disease remains poor, with few molecular targeted approaches having been successfully incorporated into routine care to date – only first line anti-HER2 therapy for ERBB2 amplification and second line anti-VEGFR2 therapy have succeeded in improving outcomes. Molecular characterization of GEC has identified other relatively frequent mutations and copy number variations in EGFR, FGFR2, MET, PI3K, and other oncogenes, candidate biomarkers, and immuno-oncologic checkpoints that may serve as actionable therapeutic targets. Here we review these key aberrations, their impact on protein expression, therapeutic implications, and potential future clinical directions within each pathway.