Medical Oncology Unit, Universita Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I - GM Lancisi - G Salesi, Ancona, Italy.
Onco Targets Ther. 2013 May 21;6:563-76. doi: 10.2147/OTT.S28155. Print 2013.
In the last decade, better understanding of the role of epidermal growth factor receptor in the pathogenesis and progression of non-small cell lung cancer has led to a revolution in the work-up of these neoplasms. Tyrosine kinase inhibitors, such as erlotinib and gefitinib, have been approved for the treatment of non-small cell lung cancer, demonstrating an improvement in progression-free and overall survival, particularly in patients harboring activating EGFR mutations. Nevertheless, despite initial responses and long-lasting remissions, resistance to tyrosine kinase inhibitors invariably develops, most commonly due to the emergence of secondary T790M mutations or to the amplification of mesenchymal-epithelial transition factor (c-Met), which inevitably leads to treatment failure. Several clinical studies are ongoing (http://www.clinicaltrials.gov), aimed to evaluate the efficacy and toxicity of combined approaches and to develop novel irreversible or multitargeted tyrosine kinase inhibitors and mutant-selective inhibitors to overcome such resistance. This review is an overview of ongoing Phase I, II, and III trials of novel small molecule epidermal growth factor receptor inhibitors and combinations in non-small cell lung cancer patients.
在过去的十年中，对表皮生长因子受体在非小细胞肺癌的发病机制和进展中的作用的更好理解，导致了这些肿瘤的研究发生了革命性的变化。酪氨酸激酶抑制剂，如厄洛替尼和吉非替尼，已被批准用于治疗非小细胞肺癌，显示出无进展生存期和总生存期的改善，特别是在携带激活的表皮生长因子受体突变的患者中。然而，尽管最初有反应和持久缓解，但不可避免地会出现对酪氨酸激酶抑制剂的耐药性，最常见的原因是继发 T790M 突变的出现或间质上皮转化因子（c-Met）的扩增，这不可避免地导致治疗失败。目前正在进行多项临床研究（http://www.clinicaltrials.gov），旨在评估联合治疗方法的疗效和毒性，并开发新型不可逆或多靶点酪氨酸激酶抑制剂和突变体选择性抑制剂，以克服这种耐药性。这篇综述概述了正在进行的 I 期、II 期和 III 期新型小分子表皮生长因子受体抑制剂和联合治疗非小细胞肺癌患者的试验。
