Kato Taketo, Tanaka Ichidai, Huang Heng, Okado Shoji, Imamura Yoshito, Nomata Yuji, Takenaka Hirofumi, Watanabe Hiroki, Kawasumi Yuta, Nakanishi Keita, Kadomatsu Yuka, Ueno Harushi, Nakamura Shota, Mizuno Tetsuya, Chen-Yoshikawa Toyofumi Fengshi
Department of Thoracic Surgery, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan.
Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan.
Int J Mol Sci. 2025 May 1;26(9):4299. doi: 10.3390/ijms26094299.
Mesothelioma is characterized by the inactivation of tumor suppressor genes, with frequent mutations in neurofibromin 2 (), BRCA1-associated protein 1 (), and cyclin-dependent kinase inhibitor 2A (). These mutations lead to disruptions in the Hippo signaling pathway and histone methylation, thereby promoting tumor growth. mutations result in Merlin deficiency, leading to uncontrolled cell proliferation, whereas mutations impair chromatin remodeling and hinder DNA damage repair. Emerging molecular targets in mesothelioma include mesothelin (), oxytocin receptor (), protein arginine methyltransferase (), and carbohydrate sulfotransferase 4 (). -based therapies, such as antibody-drug conjugates and immunotoxins, have shown efficacy in clinical trials. , upregulated in mesothelioma, is correlated with poor prognosis and represents a novel therapeutic target. inhibition is being explored in tumors with deletions, commonly co-occurring with loss. expression is associated with improved prognosis, potentially influencing tumor immunity. Immune checkpoint inhibitors targeting PD-1/PD-L1 have shown promise in some cases; however, resistance mechanisms remain a challenge. Advances in multi-omics approaches have improved our understanding of mesothelioma pathogenesis. Future research will aim to identify novel therapeutic targets and personalized treatment strategies, particularly in the context of epigenetic therapy and combination immunotherapy.
间皮瘤的特征是肿瘤抑制基因失活,神经纤维瘤蛋白2()、BRCA1相关蛋白1()和细胞周期蛋白依赖性激酶抑制剂2A()频繁发生突变。这些突变导致Hippo信号通路和组蛋白甲基化紊乱,从而促进肿瘤生长。突变导致Merlin缺乏,导致细胞增殖失控,而突变则损害染色质重塑并阻碍DNA损伤修复。间皮瘤中新兴的分子靶点包括间皮素()、催产素受体()、蛋白质精氨酸甲基转移酶()和碳水化合物磺基转移酶4()。基于的疗法,如抗体药物偶联物和免疫毒素,在临床试验中已显示出疗效。在间皮瘤中上调,与预后不良相关,是一个新的治疗靶点。在常见与缺失同时发生的缺失肿瘤中正在探索抑制作用。表达与预后改善相关,可能影响肿瘤免疫。靶向PD-1/PD-L1的免疫检查点抑制剂在某些情况下已显示出前景;然而,耐药机制仍然是一个挑战。多组学方法的进展提高了我们对间皮瘤发病机制的理解。未来的研究旨在确定新的治疗靶点和个性化治疗策略,特别是在表观遗传治疗和联合免疫治疗方面。