Sharma Sreenath V, Bell Daphne W, Settleman Jeffrey, Haber Daniel A
Massachusetts General Hospital Cancer Center and Harvard Medical School, 149 13th Street, Charlestown, Massachusetts 02129, USA.
Nat Rev Cancer. 2007 Mar;7(3):169-81. doi: 10.1038/nrc2088.
The development and clinical application of inhibitors that target the epidermal growth factor receptor (EGFR) provide important insights for new lung cancer therapies, as well as for the broader field of targeted cancer therapies. We review the results of genetic, biochemical and clinical studies focused on somatic mutations of EGFR that are associated with the phenomenon of oncogene addiction, describing 'oncogenic shock' as a mechanistic explanation for the apoptosis that follows the acute treatment of susceptible cells with kinase inhibitors. Understanding the genetic heterogeneity of epithelial tumours and devising strategies to circumvent their rapid acquisition of resistance to targeted kinase inhibitors are essential to the successful use of targeted therapies in common epithelial cancers.
靶向表皮生长因子受体（EGFR）的抑制剂的研发及临床应用为肺癌新疗法以及更广泛的靶向癌症治疗领域提供了重要见解。我们综述了聚焦于与致癌基因成瘾现象相关的EGFR体细胞突变的遗传学、生物化学及临床研究结果，将“致癌性休克”描述为用激酶抑制剂急性处理敏感细胞后发生凋亡的一种机制性解释。了解上皮性肿瘤的基因异质性并设计策略以规避其对靶向激酶抑制剂的快速耐药，对于在常见上皮性癌症中成功应用靶向治疗至关重要。
