间变性淋巴瘤激酶 (ALK)（一种酪氨酸激酶受体）的融合和突变已在多种肿瘤疾病中被发现。重排的 ALK 是肿瘤发生的驱动因素，可激活与增殖和存活相关的各种信号通路。迄今为止，已经开发出多种靶向和抑制 ALK 的药物。研究最多的 ALK 阳性疾病是非小细胞肺癌，三代 ALK 酪氨酸激酶抑制剂 (TKI) 已被批准用于治疗转移性疾病。然而，ALK-TKIs 的使用与获得性耐药（耐药突变、旁路信号传导）相关，这会导致疾病进展，并可能需要替代或引入其他治疗药物。了解耐药突变的复杂性质和网络可能有助于引入序贯和靶向治疗。在这篇综述中，我们旨在总结 ALK 抑制剂的功效和安全性，描述脱靶抗癌作用，并讨论个性化肿瘤学背景下的耐药机制。版权所有 © 2023 Kiełbowski、Żychowska 和 Becht。

Fusions and mutations of anaplastic lymphoma kinase (ALK), a tyrosine kinase receptor, have been identified in several neoplastic diseases. Rearranged ALK is a driver of tumorigenesis, which activates various signaling pathway associated with proliferation and survival. To date, several agents that target and inhibit ALK have been developed. The most studied ALK-positive disease is non-small cell lung cancer, and three generations of ALK tyrosine kinase inhibitors (TKIs) have been approved for the treatment of metastatic disease. Nevertheless, the use of ALK-TKIs is associated with acquired resistance (resistance mutations, bypass signaling), which leads to disease progression and may require a substitution or introduction of other treatment agents. Understanding of the complex nature and network of resistance mutations may allow to introduce sequential and targeted therapies. In this review, we aim to summarize the efficacy and safety profile of ALK inhibitors, describe off-target anticancer effects, and discuss resistance mechanisms in the context of personalized oncology.Copyright © 2023 Kiełbowski, Żychowska and Becht.