Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA.
J Clin Oncol. 2013 Mar 10;31(8):1105-11. doi: 10.1200/JCO.2012.44.5353. Epub 2013 Feb 11.
In 2007, scientists discovered that anaplastic lymphoma kinase (ALK) gene rearrangements are present in a small subset of non-small-cell lung cancers. ALK-positive cancers are highly sensitive to small-molecule ALK kinase inhibitors, such as crizotinib. Phase I and II studies of crizotinib in ALK-positive lung cancer demonstrated impressive activity and clinical benefit, leading to rapid US Food and Drug Administration approval in 2011. Although crizotinib induces remissions and extends the lives of patients, cures are not achieved as resistance to therapy develops. In this review, we will discuss the history of this field, current diagnostic and treatment practices, and future challenges and opportunities to advance outcomes for patients with ALK-positive lung cancers.
2007 年，科学家发现间变性淋巴瘤激酶（ALK）基因重排在一小部分非小细胞肺癌中存在。ALK 阳性癌症对小分子 ALK 激酶抑制剂如克唑替尼非常敏感。ALK 阳性肺癌的克唑替尼的 I 期和 II 期研究显示出令人印象深刻的活性和临床获益，导致 2011 年迅速获得美国食品和药物管理局的批准。尽管克唑替尼诱导缓解并延长了患者的生命，但由于对治疗的耐药性的出现，并没有实现治愈。在这篇综述中，我们将讨论这一领域的历史、当前的诊断和治疗实践，以及未来为 ALK 阳性肺癌患者改善预后的挑战和机遇。
