Maione Paolo, Sacco Paola C, Casaluce Francesca, Sgambato Assunta, Santabarbara Giuseppe, Rossi Antonio, Gridelli Cesare
Paolo Maione, MD, Division of Medical Oncology, "S. G. Moscati" Hospital, Avellino, Italy.
Rev Recent Clin Trials. 2016;11(2):99-105. doi: 10.2174/1574887111666160330120431.
The clarification of several molecular pathways underlying the tumorigenesis has led to the development of several targeted drugs that have substantially improved the treatment of Non-Small-Cell Lung Cancer (NSCLC). The Epidermal Growth Factor Receptor (EGFR) is the target of several Tyrosine-Kinase Inhibitors (TKIs), some of them approved for treatment and others currently in clinical development. EGFR-TKIs markedly improve progression-free survival of patients with advanced NSCLC with EGFR mutations compared with chemotherapy.
We undertook a structured search of bibliographic databases for peer-reviewed research literature using a focused review question.
Although first- and second-generation agents offer in target population (with EGFR mutations) a substantial improvement of outcomes compared with standard chemotherapy, unfortunately, drug resistance develops after initial benefit, through a variety of mechanisms. Novel- (third) generation EGFR inhibitors have a selective mechanism of action and are currently in advanced clinical development, producing encouraging results in patients with acquired resistance to previous generation agents.
The search for new drugs or strategies to overcome the TKI resistance in patients with EGFR mutations is to be considered a priority for the improvement of outcomes in the treatment of advanced NSCLC, and third-generation EGFR inhibitors are the most promising approach to the issue.
对肿瘤发生所涉及的多种分子途径的阐明促使了多种靶向药物的研发，这些药物显著改善了非小细胞肺癌（NSCLC）的治疗。表皮生长因子受体（EGFR）是多种酪氨酸激酶抑制剂（TKIs）的靶点，其中一些已获批用于治疗，另一些目前正处于临床开发阶段。与化疗相比，EGFR-TKIs显著提高了具有EGFR突变的晚期NSCLC患者的无进展生存期。
我们使用聚焦的综述问题对文献数据库进行了结构化检索，以查找经同行评审的研究文献。
尽管第一代和第二代药物在目标人群（具有EGFR突变）中与标准化疗相比显著改善了治疗结果，但不幸的是，在初始获益后会通过多种机制产生耐药性。新型（第三代）EGFR抑制剂具有选择性作用机制，目前正处于临床开发后期，在对前一代药物产生获得性耐药的患者中取得了令人鼓舞的结果。
寻找克服EGFR突变患者中TKI耐药性的新药或策略应被视为改善晚期NSCLC治疗结果的优先事项，而第三代EGFR抑制剂是解决该问题最有前景的方法。
