New strategies for treatment of ALK-rearranged non-small cell lung cancers.
New strategies for treatment of ALK-rearranged non-small cell lung cancers.
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DOI：
10.1158/1078-0432.ccr-11-1404
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发表时间：
2011-12-01
期刊：
影响因子：
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通讯作者：
Jänne PA
中科院分区：
文献类型：
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作者：
Sasaki T;Jänne PA
非小细胞肺癌（NSCLC）亚群中致癌改变的鉴定正在改变临床护理。在3 - 7%的非小细胞肺癌患者中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（crizotinib）在ALK重排NSCLC患者中显示出临床疗效，并于近期获得FDA批准。克唑替尼目前正处于III期临床开发阶段，作为晚期ALK重排NSCLC的一线和二线治疗药物。然而，在这一非小细胞肺癌亚群的诊断和治疗方面出现了新的挑战。其中包括诊断ALK重排NSCLC的最有效手段和对克里唑替尼获得性耐药的出现。在这篇综述中，我们将回顾目前的治疗和诊断以及目前对克里唑替尼获得性耐药机制的了解，并讨论目前正在进行的临床克服获得性耐药的策略。
The identification of oncogenic alterations in subsets of non-small cell lung cancers (NSCLC) is transforming clinical care. Genomic rearrangements in the anaplastic lymphoma kinase (ALK) are detected in 3 to 7% of NSCLC patients. The ALK tyrosine kinase inhibitor crizotinib has demonstrated clinical efficacy in ALK rearranged NSCLC patients and was recently approved by the FDA. 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. These include the most effective means of diagnosing ALK rearranged NSCLC and the emergence of acquired drug resistance to crizotinib. In this review we will review current treatment and diagnosis as well as the present knowledge on acquired resistance mechanisms to crizotinib and discuss the strategies presently underway to clinically overcome acquired drug resistance.