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大约30年前,表皮生长因子受体(epithelial growth factor receptor,EGFR)被认为是癌症治疗较为合适的靶点[1-2]。随后,肿瘤学家尝试去观察部分恶性肿瘤细胞的增殖是否依赖于EGFR的激活以及相应细胞内酪氨酸激酶下游信号的传递。针对该增殖信号通路的药物如酪氨酸激酶抑制剂(tyrosine kinase inhibitors,TKIs)在不同恶性肿瘤中作用的研究结果发现:偶尔在非小细胞癌患者中可以观察到患者对该类药物具有良好应答[3]。各种临床因素(如亚裔、非吸烟者、女性)[4-7]以及分子生物学因素(如EGFR蛋白表达量,EGFR拷贝数)曾被认为是这一选择性优势的原因[8-10]。后来人们认识到EGFR酪氨酸激酶域突变(mutations in the kinase domain of the EGFR,EGFR-MT)可能是引起这些良好应答的主要原因[11-14]。
About 30 years ago, epithelial growth factor receptor (EGFR) is considered as a more suitable target for cancer treatment [1-2]. Subsequently, oncologists try to see whether the proliferation of some malignant cells depends on the activation of EGFR and the signaling of the corresponding intracellular tyrosine kinase. A study of the effects of drugs such as tyrosine kinase inhibitors (TKIs) on this proliferation signaling pathway in different malignancies found that patients occasionally observed good non-small cell lung cancer Answer [3]. Various clinical factors (such as Asian, non-smoker, female) [4-7] and molecular biology factors such as EGFR protein expression and EGFR copy number have been considered as the reason for this selective advantage [8- 10]. It was later recognized that mutations in the kinase domain of the EGFR (EGFR-MT) may be responsible for these good responses [11-14].