恶性胸膜间皮瘤靶向治疗的研究进展  

Advances in Targeted Therapy for Malignant Pleural Mesothelioma

作　　者：傅芬 张扬[1] 沈红[1] Fen FU;Yang ZHANG;Hong SHEN(Department of Respiratory and Critical Care Medicine,The Second Affiliated Hospital of Nanjing Medical University,Nanjing 210011,China)

机构地区：[1]南京医科大学第二附属医院呼吸与危重症医学科,南京210011

出　　处：《中国肺癌杂志》2024年第5期391-398,共8页Chinese Journal of Lung Cancer

基　　金：南京市医学科技发展基金项目(No.YKK16226)资助。

摘　　要：恶性胸膜间皮瘤(malignant pleural mesothelioma, MPM)是侵袭性极强的罕见胸膜表面恶性肿瘤,危险因素包括吸入石棉、遗传因素、基因突变等。现有的化疗、抗血管生成治疗、免疫治疗的效果均不佳,患者的生存期极短。亟需寻找治疗MPM的潜在靶点,目前发现有基因突变靶点如BRCA1相关蛋白1(BRCA associated protein1, BAP1)和细胞周期蛋白依赖性激酶抑制剂2A(cyclin-dependent kinase 2A, CDKN2A)等;表观遗传靶点如组蛋白赖氨酸去甲基酶4A[lysine (K)-specific demethylase 4A, KDM4A]和赖氨酸特异性去甲基酶1(lysine-specific demethylase1, LSD1)等;信号蛋白靶点如葡萄糖调节蛋白78(glucose-regulated protein 78, GRP78)及信号转导和转录激活因子3(signal transducer and activator of transcription 3, STAT3)等。迄今为止,可查询的临床试验有组蛋白甲基转移酶抑制剂Tazemetostat、多聚ADP-核糖聚合酶[poly (ADP-ribose) polymerase, PARP]抑制剂Rucaparib和细胞周期蛋白依赖性激酶4/6(cyclin-dependent kinases 4 and 6, CDK4/6)抑制剂Abemaciclib的II期临床试验,以及靶向间皮素的嵌合抗原受体T细胞免疫疗法(chimeric antigen receptor T-cell immunotherapy, CAR-T)细胞胸腔注射、TEA结构域家族成员(TEA domain family member, TEAD)抑制剂VT3989和IK-930的I期临床试验,显示出一定的临床疗效。Malignant pleural mesothelioma(MPM)is a rare cancer with high malignancy and aggressiveness on the pleural,caused by the following risk factors including asbestos inhalation,genetic factors,and genetic mutation.The present chemotherapy,antiangiogenic therapy,and immunotherapy methods are ineffective and the survival time of patients is very short.There is an urgent need to find potential therapeutic targets for MPM.At present,it has been found the following types of targets:gene mutation targets such as BRCA associated protein 1(BAP1)and cyclin-dependent kinase 2A(CDKN2A);epigenetic targets such as lysine(K)-specific demethylase 4A(KDM4A)and lysine-specific demethylase 1(LSD1),and signal protein targets such as glucose-regulated protein 78(GRP78)and signal transducer and activator of transcription 3(STAT3).So far,available clinical trials include phase II clinical trials of histone methyltransferase inhibitor Tazemetostat,poly(ADPribose)polymerase(PARP)inhibitor Rucaparib and cyclin-dependent kinases 4 and 6(CDK4/6)inhibitor Abemaciclib,as well as phase I clinical trials of mesothelin-targeting chimeric antigen receptor T-cell immunotherapy(CAR-T)cell injection in the thoracic cavity and TEA domain family member(TEAD)inhibitor VT3989 and IK-930,and the results of these trials have showed certain clinical efficacy.

关 键 词：恶性胸膜间皮瘤 基因突变 表观遗传 信号蛋白 靶向治疗 

分 类 号：R734.3[医药卫生—肿瘤]