Shackelford Rodney E, Ansari Junaid M, Wei Eric X, Alexander Jonathan S, Cotelingam James
Department of Pathology, LSU Health Shreveport, Shreveport, LA, USA.
Department of Molecular & Cellular Physiology, LSU Health Sciences Center, Shreveport, LA 71130, USA.
Pharmacogenomics. 2017 Aug;18(12):1179-1192. doi: 10.2217/pgs-2017-0098. Epub 2017 Jul 26.
The ALK gene, first identified as an anaplastic large cell lymphoma driver mutation, is dysregulated in nearly 20 different human malignancies, including 3-7% of non-small-cell lung cancers (NSCLC). In NSCLC, ALK commonly fuses with the EML4, forming a constitutively active tyrosine kinase that drives oncogenic progression. Recently, several ALK-inhibiting drugs have been developed that are more effective than standard chemotherapeutic regimens in treating advanced ALK-positive NSCLC. For this reason, molecular diagnostic testing for dysregulated ALK expression is a necessary part of identifying optimal NSCLC treatment options. Here, we review the molecular pathology of ALK-positive NSCLC, ALK molecular diagnostic techniques, ALK-targeted NSCLC treatments, and drug resistance mechanisms to ALK-targeted therapies.
ALK基因最初被鉴定为间变性大细胞淋巴瘤驱动突变，在近20种不同的人类恶性肿瘤中表达失调，包括3%-7%的非小细胞肺癌（NSCLC）。在NSCLC中，ALK通常与EML4融合，形成一种组成型活性酪氨酸激酶，驱动致癌进展。最近，已经开发出几种ALK抑制药物，在治疗晚期ALK阳性NSCLC方面比标准化疗方案更有效。因此，对ALK表达失调进行分子诊断检测是确定最佳NSCLC治疗方案的必要部分。在此，我们综述了ALK阳性NSCLC的分子病理学、ALK分子诊断技术、ALK靶向NSCLC治疗以及对ALK靶向治疗的耐药机制。
