Novel small molecule EGFR inhibitors as candidate drugs in non-small cell lung cancer.
Novel small molecule EGFR inhibitors as candidate drugs in non-small cell lung cancer.
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新型小分子 EGFR 抑制剂作为非小细胞肺癌的候选药物。
DOI：
10.2147/ott.s28155
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发表时间：
2013
影响因子：
4
通讯作者：
Cascinu S
中科院分区：
文献类型：
--
作者：
Berardi R;Santoni M;Morgese F;Ballatore Z;Savini A;Onofri A;Mazzanti P;Pistelli M;Pierantoni C;De Lisa M;Caramanti M;Pagliaretta S;Pellei C;Cascinu S
在过去的十年中，更好地了解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，导致了这些肿瘤的工作革命。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，证明了无进展生存期和总生存期的改善，特别是在携带激活EGFR突变的患者中。然而，尽管最初的反应和持久的缓解，对酪氨酸激酶抑制剂的耐药性总是发展，最常见的是由于继发性T790 M突变的出现或间充质-上皮转化因子（c-Met）的扩增，这不可避免地导致治疗失败。几项临床研究正在进行中（http：www.clinicaltrials.gov），旨在评估联合方法的功效和毒性，并开发新的不可逆或多靶点酪氨酸激酶抑制剂和多靶点选择性抑制剂以克服这种耐药性。本文综述了新型小分子表皮生长因子受体抑制剂及其联合治疗非小细胞肺癌患者的I、II、III期临床试验。
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.