Medical Center II, Department of Hematology/Oncology, Schwarzwald-Baar Clinic, Academic Teaching Hospital University of Freiburg, Villingen-Schwenningen, Germany.
Lung Cancer. 2012 Jul;77(1):2-8. doi: 10.1016/j.lungcan.2011.12.014. Epub 2012 Jan 24.
Treatment with receptor-tyrosine kinase inhibitors (TKIs) has improved progression-free and overall survival in patients with advanced non-small cell lung cancer (NSCLC). One major target for treatment with TKI is the epidermal growth factor receptor (EGFR), particularly in patients harboring activating mutations. However, despite initial responses and long lasting remissions, the development of secondary resistance inevitably leads to treatment failure. Analyzing recent data from various phase II/III trials it seems obvious that the single mode of action of gefitinib or erlotinib can provide temporary success only. Both preclinical and clinical evidence suggest that irreversible TKIs such as afatinib or PF00299804, or combined approaches using multiple kinase inhibition (e.g. EGFR and MET) and vertical inhibition by combination of small molecules and antibodies, seem to be more promising and will be the prevailing concepts to overcome secondary EGFR-TKI resistance for the near future.
针对晚期非小细胞肺癌（NSCLC）患者，受体酪氨酸激酶抑制剂（TKIs）的治疗已改善了无进展生存期和总生存期。TKI 治疗的一个主要靶点是表皮生长因子受体（EGFR），特别是在携带激活突变的患者中。然而，尽管初始反应和持久缓解，但继发性耐药的发展不可避免地导致治疗失败。分析来自各种 II/III 期试验的最新数据表明，吉非替尼或厄洛替尼的单一作用模式似乎只能提供暂时的成功。临床前和临床证据表明，不可逆的 TKI 如阿法替尼或 PF00299804，或使用多种激酶抑制（如 EGFR 和 MET）的联合方法以及小分子和抗体的垂直抑制的联合方法，似乎更有前途，并且将是克服未来短期内继发性 EGFR-TKI 耐药的主要概念。
