Wang Shasha, Shi Yuankai, Han Xiaohong
Department of Clinical Laboratory, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing 100021, China.
Department of Medical Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing 100021, China.
Zhongguo Fei Ai Za Zhi. 2020 Nov 20;23(11):1014-1022. doi: 10.3779/j.issn.1009-3419.2020.101.44.
Echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) fusion accounts for 3%-5% of non-small cell lung cancer (NSCLC) patients. With the in-depth study of the EML4-ALK driver gene, ALK inhibitors represented by crizotinib have been gradually developed and applied in the clinic. However, the response to ALK-targeted therapy is heterogeneous among different patients. Most patients with ALK-targeted therapy will inevitably develop drug resistance, leading to tumor progression. Monitoring the efficacy of patients with prognostic markers to change the treatment in time, and selecting individualized follow-up treatment according to the mechanism of drug resistance, can effectively improve the prognosis of patients. This article will review the mechanism of ALK tyrosine kinase inhibitor (ALK-TKI) resistance and related prognostic markers to discuss the prediction for ALK-targeted therapy and the choice of subsequent treatment for drug-resistant patients. .
棘皮动物微管相关蛋白样4-间变性淋巴瘤激酶（EML4-ALK）融合在非小细胞肺癌（NSCLC）患者中占3%-5%。随着对EML4-ALK驱动基因的深入研究，以克唑替尼为代表的ALK抑制剂已逐渐开发并应用于临床。然而，不同患者对ALK靶向治疗的反应存在异质性。大多数接受ALK靶向治疗的患者不可避免地会产生耐药性，导致肿瘤进展。通过监测具有预后标志物的患者的疗效来及时改变治疗方案，并根据耐药机制选择个体化的后续治疗，可以有效改善患者的预后。本文将综述ALK酪氨酸激酶抑制剂（ALK-TKI）耐药的机制及相关预后标志物，以探讨ALK靶向治疗的预测及耐药患者后续治疗的选择。
