Fu Fen, Zhang Yang, Shen Hong
Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China.
Zhongguo Fei Ai Za Zhi. 2024 May 20;27(5):391-398. doi: 10.3779/j.issn.1009-3419.2024.102.18.
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 (ADP-ribose) 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. .
恶性胸膜间皮瘤(MPM)是一种罕见的癌症,对胸膜具有高度恶性和侵袭性,由以下风险因素引起,包括吸入石棉、遗传因素和基因突变。目前的化疗、抗血管生成治疗和免疫治疗方法均无效,患者的生存时间很短。迫切需要找到MPM的潜在治疗靶点。目前,已发现以下几种类型的靶点:基因突变靶点,如BRCA相关蛋白1(BAP1)和细胞周期蛋白依赖性激酶2A(CDKN2A);表观遗传靶点,如赖氨酸(K)特异性去甲基化酶4A(KDM4A)和赖氨酸特异性去甲基化酶1(LSD1),以及信号蛋白靶点,如葡萄糖调节蛋白78(GRP78)和信号转导及转录激活因子3(STAT3)。到目前为止,可用的临床试验包括组蛋白甲基转移酶抑制剂他泽司他、聚(ADP-核糖)聚合酶(PARP)抑制剂鲁卡帕尼和细胞周期蛋白依赖性激酶4和6(CDK4/6)抑制剂阿贝西利的II期临床试验,以及间皮素靶向嵌合抗原受体T细胞免疫疗法(CAR-T)胸腔注射和TEA结构域家族成员(TEAD)抑制剂VT3989和IK-930的I期临床试验,这些试验结果已显示出一定的临床疗效。