Targeted therapies for non-small cell lung cancer: an evolving landscape.
Targeted therapies for non-small cell lung cancer: an evolving landscape.
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DOI：
10.1158/1535-7163.mct-10-0239
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发表时间：
2010-07
影响因子：
5.7
通讯作者：
Reckamp K
中科院分区：
文献类型：
--
作者：
Pal SK;Figlin RA;Reckamp K
在过去的十年中，许多靶向药物被用于晚期非小细胞肺癌（NSCLC）的治疗。到目前为止，在临床实践中已经实施了两大类药物：(1)血管内皮生长因子（VEGF）导向治疗和(2)表皮生长因子受体（EGFR）拮抗剂。在前一类中，贝伐珠单抗（一种单克隆抗体）加入细胞毒治疗后，生存率有了里程碑式的提高。靶向VEGF受体的小分子酪氨酸激酶抑制剂（TKIs）（即舒尼替尼、索拉非尼和万德替尼）在II期临床研究中显示出活性。关于egfr定向治疗，TKIs吉非替尼和厄洛替尼已显示出显着的益处，并揭示了有关肺癌生物学的宝贵信息。除了专门针对VEGF和egfr介导的信号传导的治疗外，评估胰岛素样生长因子-1受体（IGF-IR）靶向药物、环氧化酶-2 （COX-2）抑制剂、c-met抑制剂、不可逆泛her抑制剂、哺乳动物雷帕霉素靶点（mTOR）抑制剂和组蛋白去乙酰化酶（HDAC）抑制剂的试验正在进行中。ALK抑制剂在相关基因易位患者中显示出巨大的希望。本文描述了NSCLC新疗法的临床发展，包括一些相关生物标志物的讨论以及与细胞毒治疗和其他靶向药物的协同作用的确定。
Over the past decade, a multitude of targeted agents have been explored in the treatment of advanced non-small cell lung cancer (NSCLC). Thus far, two broad classes of agents have been implemented in clinical practice: (1) vascular endothelial growth factor (VEGF)-directed therapies and (2) antagonists of the epidermal growth factor receptor (EGFR). In the former category, the agent bevacizumab (a monoclonal antibody) has shown landmark improvements in survival when added to cytotoxic therapy. Small molecule tyrosine kinase inhibitors (TKIs) targeting the VEGF receptor (i.e., sunitinib, sorafenib, and vandetanib) show activity in phase II clinical studies. With respect to EGFR-directed therapies, the TKIs gefitinib and erlotinib have demonstrated significant benefit, and have uncovered valuable information regarding the biology of lung cancer. Outside of therapies directed specifically at VEGF- and EGFR-mediated signaling, trials evaluating insulin-like growth factor-1 receptor (IGF-IR)-targeting agents, cyclooxygenase-2 (COX-2) inhibitors, c-met inhibitors, irreversible pan-HER inhibitors, mammalian target of rapamycin (mTOR) inhibitors, and histone deacetylase (HDAC) inhibitors are ongoing. Inhibitors of ALK show great promise in patients with the relevant gene translocation. Herein, the clinical development of novel therapies for NSCLC is described, including some discussion of relevant biomarkers and determination of synergy with both cytotoxic therapy and other targeted agents.