洛拉替尼治疗ALK基因突变非小细胞肺癌的研究进展  

Research Progress of Lorlatinib for ALK-mutated Non-small Cell Lung Cancer

作　　者：郭晨晨 梁蔚婷[2] 徐文华[2] 张云惠 黄焕均 陈卓佳[2] GUO Chenchen;LIANG Weiting;XU Wenhua;ZHANG Yunhui;HUANG Huanjun;CHEN Zhuojia(School of Pharmacutical Sciences,Sun Yat-sen University,Guangzhou,Guangdong 510060,China;State Key Laboratory of Oncology in South China,Guangdong Provincial Clinical Research Center for Cancer,Sun Yat-sen University Cancer Center,Guangzhou,Guangdong 510060,China)

机构地区：[1]中山大学药学院,广东广州510006 [2]华南恶性肿瘤防治全国重点实验室,广东省恶性肿瘤临床医学研究中心,中山大学肿瘤防治中心,广东广州510060

出　　处：《今日药学》2024年第10期794-800,共7页Pharmacy Today

基　　金：中山大学肿瘤防治中心“青年优创”项目(PT21060101);广东省医院药学研究基金(2022-1115-28)。

摘　　要：非小细胞肺癌(NSCLC)是肺癌中最常见的一类,其中间变性淋巴瘤激酶(ALK)基因突变在基因突变的非小细胞肺癌患者中占比约5%~7%。第一、二代ALK抑制剂是治疗ALK突变NSCLC的标准方案,但治疗过程中出现的耐药及脑转移是目前临床面临的难题。洛拉替尼是近年上市的第三代ALK抑制剂,对ALK激酶域突变的临床活性广谱且高效,中枢神经渗透性更高,入脑效果更佳,对既往接受过ALK抑制剂且出现耐药的患者也存在活性,可解决一二代ALK抑制剂的耐药及脑转移效果差的问题。本文将围绕洛拉替尼治疗ALK基因突变NSCLC的作用机制、药代动力学、临床应用的疗效及安全性等各方面研究进展进行综述,以期为临床提供更深入、全面的洛拉替尼应用指导,同时为未来关于洛拉替尼的研究方向和策略提供科学依据和建议。Non-small cell lung cancer(NSCLC)is the most common type of lung cancer,of which anaplastic lymphoma kinase(ALK)gene mutation accounts for about 5%-7%of NSCLC patients with gene mutations.First-generation and second-generation ALK inhibitors are standard regimens for the treatment of ALK-mutated NSCLC,but the emergence of drug resistance and brain metastases during treatment is currently a difficult clinical problem.Lorlatinib is a third-generation ALK inhibitor marketed in recent years,with broad spectrum and high clinical activity against ALK kinase domain mutations,higher central nervous permeability,better brain entry effect,and activity in patients who have previously received ALK inhibitors and developed resistance,which can solve the problem of resistance to first-generation ALK inhibitors and poor effect on brain metastasis.This article will review the research progress in the mechanism of action,pharmacokinetics,efficacy and safety of lorlatinib in the treatment of NSCLC with ALK gene mutation,in order to provide more in-depth and comprehensive guidance for the application of lorlatinib in clinical practice,and provide scientific basis and suggestions for the future research direction and strategy of lorlatinib.

关 键 词：洛拉替尼 间变性淋巴瘤激酶 酪氨酸激酶抑制剂 非小细胞肺癌 有效性 安全性 

分 类 号：R966[医药卫生—药理学]