Lee Wen-Chin, Chiu Chien-Hua, Chu Tian-Huei, Chien Yu-Shu
Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Medical Laboratory, Medical Education and Research Center, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan.
Front Cell Dev Biol. 2022 Apr 6;10:876723. doi: 10.3389/fcell.2022.876723. eCollection 2022.
Hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) emerge as promising agents to treat anemia in chronic kidney disease (CKD) but the major concern is their correlated risk of cancer development and progression. The Wilms' tumor gene, , is transcriptionally regulated by HIF and is known to play a crucial role in tumorigenesis and invasiveness of certain types of cancers. From the mechanism of action of HIF-PHIs, to cancer hypoxia and the biological significance of WT1, this review will discuss the link between HIF, WT1, anemia correction, and cancer. We aimed to reveal the research gaps and offer a focused strategy to monitor the development and progression of specific types of cancer when using HIF-PHIs to treat anemia in CKD patients. In addition, to facilitate the long-term use of HIF-PHIs in anemic CKD patients, we will discuss the strategy of WT1 inhibition to reduce the development and progression of cancer.
缺氧诱导因子脯氨酰羟化酶抑制剂（HIF-PHIs）成为治疗慢性肾脏病（CKD）贫血的有前景的药物，但主要担忧是其与癌症发生和进展相关的风险。威尔姆斯瘤基因WT1受HIF转录调控，已知在某些类型癌症的肿瘤发生和侵袭中起关键作用。从HIF-PHIs的作用机制、癌症缺氧以及WT1的生物学意义，本综述将讨论HIF、WT1、贫血纠正和癌症之间的联系。我们旨在揭示研究空白，并提供一个重点策略，以监测在使用HIF-PHIs治疗CKD患者贫血时特定类型癌症的发生和进展。此外，为促进HIF-PHIs在贫血CKD患者中的长期使用，我们将讨论抑制WT1以减少癌症发生和进展的策略。
