文章：

ALK在癌症中的作用：从功能到治疗靶向

ALK in cancer: from function to therapeutic targeting

原文发布日期：2025-03-07

DOI: 10.1038/s41568-025-00797-9

类型: Review Article

开放获取: 否

英文摘要：

Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase (RTK) that acts as an oncogenic driver in solid and haematological malignancies in both children and adults. Although ALK-expressing (ALK+) tumours show strong initial responses to the series of ALK inhibitors currently available, many patients will develop resistance. In this Review, we discuss recent advances in ALK oncogenic signalling, together with existing and promising new modalities to treat ALK-driven tumours, including currently approved ALK-directed therapies, namely tyrosine kinase inhibitors, and novel approaches such as ALK-specific immune therapies. Although ALK inhibitors have changed the management and clinical history of ALK+ tumours, they are still insufficient to cure most of the patients. Therefore, more effort is needed to further improve outcomes and prevent the tumour resistance, recurrence and metastatic spread that many patients with ALK+ tumours experience. Here, we outline how a multipronged approach directed against ALK and other essential pathways that sustain the persistence of ALK+ tumours, together with potent or specific immunotherapies, could achieve this goal. We envision that the lessons learned from treating ALK+ tumours in the clinic could ultimately accelerate the implementation of innovative combination therapies to treat tumours driven by other tyrosine kinases or oncogenes with similar properties.

摘要翻译： 

间变性淋巴瘤激酶（ALK）是一种受体酪氨酸激酶（RTK），在儿童和成人实体瘤及血液系统恶性肿瘤中作为致癌驱动因子发挥作用。尽管表达ALK（ALK+）的肿瘤对现有系列ALK抑制剂显示出强烈的初始反应，但许多患者会产生耐药性。本篇综述中，我们将讨论ALK致癌信号传导的最新研究进展，包括现有及前景良好的ALK驱动肿瘤治疗新策略——涵盖目前已获批的ALK导向疗法（即酪氨酸激酶抑制剂）和ALK特异性免疫疗法等创新手段。虽然ALK抑制剂改变了ALK+肿瘤的治疗格局和临床病程，但仍不足以治愈大多数患者。因此，需要更多努力来进一步改善临床结局，预防ALK+肿瘤患者常见的耐药、复发和转移问题。我们在此提出，通过针对ALK及其维持肿瘤持续存在的关键通路采取多管齐下的治疗策略，并结合高效或特异性免疫疗法，可能实现这一目标。我们预见，从ALK+肿瘤临床治疗中获得的经验教训，最终将加速创新联合疗法在具有相似特性的其他酪氨酸激酶或致癌基因驱动肿瘤治疗中的应用。

原文链接：

ALK in cancer: from function to therapeutic targeting