Target Oncol. 2012 Sep;7(3):199-210. doi: 10.1007/s11523-012-0227-8. Epub 2012 Sep 12.
Anaplastic lymphoma kinase (ALK) is a tyrosine kinase receptor that affects a number of biological and biochemical functions through normal ligand-dependent signaling. It has oncogenic functions in a number of tumors including non-small cell lung cancer (NSCLC), anaplastic large cell lymphoma, and neuroblastoma when altered by translocation or amplification or mutation. On August 2011, a small molecule inhibitor against ALK, crizotinib, was approved for therapy against NSCLC with ALK translocations. As we determine the molecular heterogeneity of tumors, the potential of ALK as a relevant therapeutic target in a number of malignancies has become apparent. This review will discuss some of the tumor types with oncogenic ALK alterations. The activity and unique toxicities of crizotinib are described, along with potential mechanisms of resistance and new therapies beyond crizotinib.
间变性淋巴瘤激酶 (ALK) 是一种酪氨酸激酶受体，通过正常的配体依赖性信号转导影响许多生物学和生化功能。当发生易位、扩增或突变时，ALK 在多种肿瘤中具有致癌功能，包括非小细胞肺癌 (NSCLC)、间变大细胞淋巴瘤和神经母细胞瘤。2011 年 8 月，一种针对 ALK 的小分子抑制剂克唑替尼被批准用于治疗具有 ALK 易位的 NSCLC。随着我们确定肿瘤的分子异质性，ALK 作为多种恶性肿瘤中相关治疗靶点的潜力已经变得明显。这篇综述将讨论一些具有致癌性 ALK 改变的肿瘤类型。描述了克唑替尼的活性和独特毒性，以及克唑替尼以外的潜在耐药机制和新疗法。
