Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, PR China.
China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, PR China.
Oncogene. 2023 Jun;42(24):1959-1969. doi: 10.1038/s41388-023-02712-8. Epub 2023 May 6.
Anaplastic lymphoma kinase (ALK) is a member of the insulin receptor protein-tyrosine kinase superfamily and was first discovered in anaplastic large-cell lymphoma (ALCL). ALK alterations, including fusions, over-expression and mutations, are highly associated with cancer initiation and progression. This kinase plays an important role in different cancers, from very rare to the more prevalent non-small cell lung cancers. Several ALK inhibitors have been developed and received Food and Drug Administration (FDA) approval. However, like other drugs used in targeted therapies, ALK inhibitors inevitably encounter cancer cell resistance. Therefore, monoclonal antibody screening based on extracellular domain or combination therapies may provide viable alternatives for treating ALK-positive tumors. In this review, we discuss the current understanding of wild-type ALK and fusion protein structures, the pathological functions of ALK, ALK target therapy, drug resistance and future therapeutic directions.
间变性淋巴瘤激酶（ALK）是胰岛素受体蛋白酪氨酸激酶超家族的成员，最初在间变性大细胞淋巴瘤（ALCL）中发现。ALK 改变，包括融合、过表达和突变，与癌症的发生和进展高度相关。这种激酶在不同的癌症中发挥着重要作用，从非常罕见到更常见的非小细胞肺癌。已经开发了几种 ALK 抑制剂，并获得了美国食品和药物管理局（FDA）的批准。然而，与其他用于靶向治疗的药物一样，ALK 抑制剂不可避免地会遇到癌细胞耐药性。因此，基于细胞外结构域的单克隆抗体筛选或联合治疗可能为治疗 ALK 阳性肿瘤提供可行的替代方案。在这篇综述中，我们讨论了对野生型 ALK 和融合蛋白结构、ALK 的病理功能、ALK 靶向治疗、耐药性和未来治疗方向的现有认识。
