Dagogo-Jack I, Shaw A T, Riely G J
Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, New York, USA.
Clin Pharmacol Ther. 2017 May;101(5):625-633. doi: 10.1002/cpt.653. Epub 2017 Mar 17.
In the 9 years since the initial discovery of anaplastic lymphoma kinase (ALK) gene rearrangements in non-small cell lung cancer (NSCLC), there has been tremendous progress, culminating in an ever-expanding repertoire of agents that have activity in this disease. This review article provides an overview of currently approved ALK inhibitors, other ALK inhibitors in development, and commonly described mechanisms of resistance to ALK inhibitors. We also discuss emerging controversies in treatment of patients with ALK-positive lung cancer, including the choice of first-line ALK inhibitor and the role of tyrosine kinase inhibitors in the treatment of central nervous system metastases.
自首次在非小细胞肺癌(NSCLC)中发现间变性淋巴瘤激酶(ALK)基因重排以来的9年里,已经取得了巨大进展,最终形成了在该疾病中具有活性的不断扩大的药物库。这篇综述文章概述了目前已获批的ALK抑制剂、其他正在研发的ALK抑制剂以及常见的ALK抑制剂耐药机制。我们还讨论了ALK阳性肺癌患者治疗中出现的争议,包括一线ALK抑制剂的选择以及酪氨酸激酶抑制剂在中枢神经系统转移治疗中的作用。