Medical Oncology, Department of Experimental and Internal Medicine "F. Magrassi", University of Campania "Luigi Vanvitelli", via S. Pansini 5, 80131, Naples, Italy.
Mol Cancer. 2018 Feb 19;17(1):30. doi: 10.1186/s12943-018-0776-2.
Anaplastic lymphoma kinase (ALK) gene activation is involved in the carcinogenesis process of several human cancers such as anaplastic large cell lymphoma, lung cancer, inflammatory myofibroblastic tumors and neuroblastoma, as a consequence of fusion with other oncogenes (NPM, EML4, TIM, etc) or gene amplification, mutation or protein overexpression. ALK is a transmembrane tyrosine kinase receptor that, upon ligand binding to its extracellular domain, undergoes dimerization and subsequent autophosphorylation of the intracellular kinase domain. When activated in cancer it represents a target for specific inhibitors, such as crizotinib, ceritinib, alectinib etc. which use has demonstrated significant effectiveness in ALK-positive patients, in particular ALK-positive non- small cell lung cancer. Several mechanisms of resistance to these inhibitors have been described and new strategies are underway to overcome the limitations of current ALK inhibitors.
间变性淋巴瘤激酶（ALK）基因的激活涉及多种人类癌症的癌变过程，如间变大细胞淋巴瘤、肺癌、炎性肌纤维母细胞瘤和神经母细胞瘤，其原因是与其他癌基因（NPM、EML4、TIM 等）融合或基因扩增、突变或蛋白过表达。ALK 是一种跨膜酪氨酸激酶受体，当配体与其细胞外结构域结合时，它会发生二聚化，随后细胞内激酶结构域发生自身磷酸化。在癌症中被激活时，它成为特定抑制剂的靶标，例如克唑替尼、色瑞替尼、阿来替尼等，这些抑制剂的使用已证明在 ALK 阳性患者中具有显著疗效，特别是在 ALK 阳性非小细胞肺癌中。已经描述了几种对这些抑制剂的耐药机制，并且正在采取新的策略来克服当前 ALK 抑制剂的局限性。
