Xu Nuo, Tong Yun, Ma Kexin, Jiang Lihan, Zheng Wenjie
Department of Oncology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China.
Med Oncol. 2025 Jul 20;42(8):352. doi: 10.1007/s12032-025-02912-0.
Patients with advanced hepatocellular carcinoma are treated using conventional therapeutic approaches and a variety of molecularly targeted drugs. Nevertheless, therapeutic resistance emerges because of the high heterogeneity of the malignancy, often restricting the effectiveness of these interventions. Therefore, therapeutic resistance represents a significant obstacle in managing liver cancer. Ubiquitination and deubiquitination, essential regulatory mechanisms, regulate the activity of diverse proteins and are pivotal in determining tumor therapeutic resistance. In this review, we focus on the enzymes involved in ubiquitination and deubiquitination in hepatocellular carcinoma, examining their associated phenotypes. Furthermore, we synthesize findings from a range of studies to elucidate the mechanisms of therapeutic resistance in hepatocellular carcinoma and highlight the critical role of ubiquitination and deubiquitination enzymes in these processes. Finally, we explore the therapeutic potential of targeting the ubiquitination and deubiquitination systems to enhance drug efficacy in liver cancer treatment significantly.
晚期肝细胞癌患者采用传统治疗方法和多种分子靶向药物进行治疗。然而，由于恶性肿瘤的高度异质性，治疗耐药性出现，常常限制了这些干预措施的有效性。因此，治疗耐药性是肝癌治疗中的一个重大障碍。泛素化和去泛素化是重要的调节机制，可调节多种蛋白质的活性，在决定肿瘤治疗耐药性方面起着关键作用。在本综述中，我们聚焦于肝细胞癌中参与泛素化和去泛素化的酶，研究它们相关的表型。此外，我们综合一系列研究的结果，以阐明肝细胞癌治疗耐药性的机制，并强调泛素化和去泛素化酶在这些过程中的关键作用。最后，我们探索靶向泛素化和去泛素化系统以显著提高肝癌治疗中药物疗效的治疗潜力。
