Neves Sara P, Bomfim Larissa M, Bezerra Daniel P
Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ/BA), Salvador, Bahia, Brazil.
Cell Death Dis. 2025 Sep 1;16(1):666. doi: 10.1038/s41419-025-07983-5.
Hepatocellular carcinoma (HCC) is the most common type of liver cancer, accounting for over 90% of all cases. Patients with advanced-stage HCC are referred to systemic treatment. Although some advances in HCC therapy have been made in recent years, the prognosis for patients remains poor due to drug resistance, tumor relapse, and metastasis, implying that overall survival remains a challenge. Many studies have shown that tumor-initiating stem cells, also known as cancer stem cells (CSCs), play essential roles in tumorigenesis, metastasis, and treatment resistance in HCC and that future cancer treatments could be significantly improved by targeting this cell population subset. Different markers of CSCs from HCC have been identified, and intracellular signaling pathways and extracellular factors have been reported as targets capable of removing this cell subpopulation, highlighting the possibility of developing targeted drugs to eradicate HCC CSCs. In this review, we highlight emerging small compounds that target HCC CSCs to provide new insights and guide future research. Drugs in the preclinical and clinical trial development stages were selected and discussed.
肝细胞癌（HCC）是最常见的肝癌类型，占所有病例的90%以上。晚期HCC患者需接受全身治疗。尽管近年来HCC治疗取得了一些进展，但由于耐药性、肿瘤复发和转移，患者的预后仍然很差，这意味着总体生存率仍然是一个挑战。许多研究表明，肿瘤起始干细胞，也称为癌症干细胞（CSCs），在HCC的肿瘤发生、转移和治疗耐药中起重要作用，并且通过靶向这一细胞亚群，未来的癌症治疗可能会得到显著改善。已鉴定出HCC中CSCs的不同标志物，并且细胞内信号通路和细胞外因子已被报道为能够去除这一细胞亚群的靶点，这突出了开发靶向药物以根除HCC CSCs的可能性。在本综述中，我们重点介绍了针对HCC CSCs的新兴小分子化合物，以提供新的见解并指导未来的研究。我们选择并讨论了处于临床前和临床试验开发阶段的药物。
