C-ros原癌基因1-受体酪氨酸激酶重排非小细胞肺癌药物治疗进展  

Research progress on the drug therapy with C-ros proto-oncogene 1-receptor tyrosine kinase rearrangement in non-small cell lung cancer

作　　者：陈书杨 卞延东 于明鑫 于国华[2] CHEN Shuyang;BIAN Yandong;YU Mingxin;YU Guohua(School of Clinical Medicine,Shandong Second Medical University,Shandong Weifang 261053,China;Department of Oncology,Weifang People's Hospital,Shandong Weifang 261044,China)

机构地区：[1]山东第二医科大学临床医学院,山东潍坊261053 [2]潍坊市人民医院肿瘤内科,山东潍坊261044

出　　处：《临床药物治疗杂志》2024年第8期6-12,共7页Clinical Medication Journal

基　　金：潍坊市卫生健康委员会科研项目(WFWSJK-2023-293)。

摘　　要：C-ros原癌基因1-受体酪氨酸激酶(ROS1)重排发生在0.9%~2.6%的非小细胞肺癌(NSCLC)中,治疗主要为靶向治疗、化学治疗及免疫治疗。靶向治疗是临床最常用的治疗方法且疗效明确,在ROS1重排NSCLC中使用酪氨酸激酶抑制剂(TKI)可显著改善预后。目前用于ROS1重排NSCLC一线治疗的克唑替尼和恩曲替尼均易产生耐药,因此针对克唑替尼的耐药位点,已研发出对其敏感的后代TKI,如洛拉替尼、洛普替尼、卡博替尼、布格替尼、他雷替尼。随着新一代TKI颅内疗效的改善,塞瑞替尼和洛拉替尼有望成为一线治疗选择,但仍需加强研究。所有患者在TKI治疗下都会出现疾病进展,因此了解获得性耐药机制对确定最佳序贯治疗至关重要。在TKI治疗失败后,探索免疫-化疗组合的潜在疗效成为临床研究的新方向。本文就ROS1重排NSCLC患者的相关治疗方法(靶向治疗、化学治疗、免疫治疗)及其研究进展进行综述,以期为临床治疗提供参考。C-ros proto-oncogene 1-receptor tyrosine kinase(ROS1)rearrangement occurs in 0.9%to 2.6%of non-small cell lung cancers(NSCLC),and the main treatments are targeted therapy,chemotherapy,and immunotherapy.Targeted therapies are the most commonly used therapies with clear efficacy,and the use of tyrosine kinase inhibitor(TKI)in ROS1-rearranged NSCLC can significantly improve the prognosis.Both crizotinib and entrectinib,which are currently used in the first-line treatment of ROS1-rearranged NSCLC,are prone to drug resistance,so progeny TKI that are sensitive to crizotinib have been developed for the resistance site of crizotinib,such as lorlatinib,repotrectinib,brigatinib,cabozantinib and taletrectinib.With the improved intracranial efficacy of the new generation of TKI,ceritinib and loratinib are expected to become first-line treatment options,but further studies are still needed.All patients will experience disease progression with TKI therapy,so understanding the mechanisms of acquired resistance is critical to determining the best sequential therapy.After TKI failure,exploring the potential efficacy of immuno-chemotherapy combinations has become a new direction for clinical research.This article reviews the relevant therapeutic approaches(targeted therapy,chemotherapy,immunotherapy)and their research progress in patients with ROS1-rearranged NSCLC in order,to provide a reference for clinical treatment.

关 键 词：C-ros原癌基因1-受体酪氨酸激酶重排 非小细胞肺癌 靶向药物 免疫治疗 获得性耐药 

分 类 号：R979.1[医药卫生—药品] R734.2[医药卫生—药学]