肺癌当前分子靶向治疗面临的临床挑战
Clinical Challenges to Current Molecularly Targeted Therapies in Lung Cancer.
作者信息
Chhabra Gagan, Eggert Ashley, Puri Neelu
机构信息
Department of Biomedical Sciences, University of Illinois College of Medicine, Rockford, Illinois, USA.
出版信息
Arch Cancer Res. 2015;3(3). doi: 10.21767/2254-6081.100030.
Lung cancer is difficult to treat with a poor prognosis and a five year survival of 15%. Current molecularly targeted therapies are initially effective in non-small cell lung cancer (NSCLC) patients; however, they are plagued with difficulties including induced resistance and small therapeutically responsive populations. This mini review describes the mechanism of resistance to several molecularly targeted therapies which are currently being used to treat NSCLC. The major targets discussed are c-Met, EGFR, HER2, ALK, VEGFR, and BRAF. The first generation tyrosine kinase inhibitors (TKIs) resulted in resistance; however, second and third generation TKIs are being developed, which are generally more efficacious and have potential to treat NSCLC patients with resistance to first generation TKIs. Combination therapies could also be effective in preventing TKI resistance in NSCLC patients.
肺癌难以治疗，预后较差，五年生存率为15%。目前的分子靶向疗法最初对非小细胞肺癌（NSCLC）患者有效；然而，它们存在诸多困难，包括诱导耐药性和治疗反应性小的群体。这篇小型综述描述了目前用于治疗NSCLC的几种分子靶向疗法的耐药机制。讨论的主要靶点是c-Met、表皮生长因子受体（EGFR）、人表皮生长因子受体2（HER2）、间变性淋巴瘤激酶（ALK）、血管内皮生长因子受体（VEGFR）和B-Raf原癌基因（BRAF）。第一代酪氨酸激酶抑制剂（TKIs）产生了耐药性；然而，第二代和第三代TKIs正在研发中，它们通常更有效，并且有潜力治疗对第一代TKIs耐药的NSCLC患者。联合疗法在预防NSCLC患者的TKI耐药性方面也可能有效。
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