Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.
Clin Cancer Res. 2011 Dec 1;17(23):7213-8. doi: 10.1158/1078-0432.CCR-11-1404. Epub 2011 Oct 18.
The identification of oncogenic alterations in subsets of patients with non-small cell lung cancer (NSCLC) is transforming clinical care. Genomic rearrangements in anaplastic lymphoma kinase (ALK) are detected in 3% to 7% of patients with NSCLC. The ALK tyrosine kinase inhibitor crizotinib has demonstrated clinical efficacy in ALK-rearranged NSCLC patients and was recently approved by the U.S. Food and Drug Administration. Crizotinib is currently under additional phase III clinical development as both initial and second-line therapy for advanced ALK-rearranged NSCLC. However, new challenges in the diagnosis and treatment of this subset of NSCLC have emerged, including the need to determine the most effective means of diagnosing ALK-rearranged NSCLC and the emergence of acquired drug resistance to crizotinib. In this review, we discuss current strategies for treatment and diagnosis, as well as the current knowledge about mechanisms of acquired resistance to crizotinib. Finally, we discuss the strategies that are underway to clinically overcome acquired drug resistance.
在非小细胞肺癌（NSCLC）的某些患者亚群中，鉴定致癌改变正在改变临床护理。在 3%至 7%的 NSCLC 患者中可检测到间变性淋巴瘤激酶（ALK）的基因组重排。ALK 酪氨酸激酶抑制剂克唑替尼在 ALK 重排的 NSCLC 患者中显示出临床疗效，最近已被美国食品和药物管理局批准。克唑替尼目前正在进行额外的 III 期临床开发，作为晚期 ALK 重排 NSCLC 的一线和二线治疗。然而，在这一组 NSCLC 的诊断和治疗中出现了新的挑战，包括需要确定诊断 ALK 重排 NSCLC 的最有效方法，以及对克唑替尼获得性耐药的出现。在这篇综述中，我们讨论了当前的治疗和诊断策略，以及关于克唑替尼获得性耐药机制的现有知识。最后，我们讨论了正在进行的克服获得性药物耐药性的策略。
