Huynh Kenneth N, Rao Sriram, Roth Bradley, Bryan Theodore, Fernando Dayantha M, Dayyani Farshid, Imagawa David, Abi-Jaoudeh Nadine
Division of Interventional Radiology, Department of Radiological Sciences, University of California Irvine, Orange, CA 92868, USA.
Division of Hematology and Oncology, Department of Medicine, Chao Family Comprehensive Cancer Center, University of California Irvine, Orange, CA 92868, USA.
Cancers (Basel). 2023 May 12;15(10):2738. doi: 10.3390/cancers15102738.
Hypoxia-inducible factor 1 alpha (HIF-1α) is a transcription factor that regulates the cellular response to hypoxia and is upregulated in all types of solid tumor, leading to tumor angiogenesis, growth, and resistance to therapy. Hepatocellular carcinoma (HCC) is a highly vascular tumor, as well as a hypoxic tumor, due to the liver being a relatively hypoxic environment compared to other organs. Trans-arterial chemoembolization (TACE) and trans-arterial embolization (TAE) are locoregional therapies that are part of the treatment guidelines for HCC but can also exacerbate hypoxia in tumors, as seen with HIF-1α upregulation post-hepatic embolization. Hypoxia-activated prodrugs (HAPs) are a novel class of anticancer agent that are selectively activated under hypoxic conditions, potentially allowing for the targeted treatment of hypoxic HCC. Early studies targeting hypoxia show promising results; however, further research is needed to understand the effects of HAPs in combination with embolization in the treatment of HCC. This review aims to summarize current knowledge on the role of hypoxia and HIF-1α in HCC, as well as the potential of HAPs and liver-directed embolization.
缺氧诱导因子1α（HIF-1α）是一种转录因子，可调节细胞对缺氧的反应，在所有类型的实体瘤中均上调，导致肿瘤血管生成、生长及对治疗产生抗性。肝细胞癌（HCC）是一种血管丰富的肿瘤，也是一种缺氧肿瘤，因为与其他器官相比，肝脏是一个相对缺氧的环境。经动脉化疗栓塞术（TACE）和经动脉栓塞术（TAE）是局部治疗方法，是HCC治疗指南的一部分，但也会加剧肿瘤缺氧，如肝栓塞后HIF-1α上调所见。缺氧激活前体药物（HAPs）是一类新型抗癌药物，在缺氧条件下被选择性激活，可能实现对缺氧HCC的靶向治疗。早期针对缺氧的研究显示出有前景的结果；然而，需要进一步研究以了解HAPs与栓塞联合治疗HCC的效果。本综述旨在总结目前关于缺氧和HIF-1α在HCC中的作用以及HAPs和肝靶向栓塞潜力的知识。
