Romanidou Ourania, Landi Lorenza, Cappuzzo Federico, Califano Raffaele
Cancer Research UK Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK, and Medical Oncology Unit, Papageorgiou General Hospital, Thessaloniki, Greece.
Department of Medical Oncology, University Hospital of South Manchester NHS Foundation Trust, Manchester, UK.
Ther Adv Med Oncol. 2016 May;8(3):176-87. doi: 10.1177/1758834016631531. Epub 2016 Feb 16.
Epidermal growth factor receptor (EGFR) activating mutations and anaplastic lymphoma kinase (ALK) gene rearrangement in advanced non-small cell lung cancer (NSCLC) represent the two oncogenic events with an impact on current clinical practice. EGFR tyrosine kinase inhibitors (TKIs) and crizotinib are the standard of care for the treatment of EGFR mutant and ALK gene rearranged advanced NSCLC patients. Unfortunately, despite initial clinical benefit, acquired resistance to EGFR-TKIs or crizotinib usually develops after an average of 10-12 months of treatment. The aim of this review is to describe the mechanisms of resistance to first/second generation EGFR-TKIs and crizotinib. In particular, we focus on strategies to overcome resistance due to secondary EGFR T790M mutation and mutations of the ALK domain.
表皮生长因子受体（EGFR）激活突变和间变性淋巴瘤激酶（ALK）基因重排是晚期非小细胞肺癌（NSCLC）中影响当前临床实践的两种致癌事件。EGFR酪氨酸激酶抑制剂（TKIs）和克唑替尼是治疗EGFR突变型和ALK基因重排的晚期NSCLC患者的标准治疗方法。不幸的是，尽管最初有临床获益，但对EGFR-TKIs或克唑替尼的获得性耐药通常在平均治疗10-12个月后出现。本综述的目的是描述对第一代/第二代EGFR-TKIs和克唑替尼的耐药机制。特别是，我们重点关注克服因EGFR T790M继发性突变和ALK结构域突变导致的耐药的策略。
