Leung Rainbow Wing Hei, Lee Terence Kin Wah
Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, China.
State Key Laboratory of Chemical Biology and Drug Discovery, The Hong Kong Polytechnic University, Hong Kong, China.
Cancers (Basel). 2022 Nov 7;14(21):5468. doi: 10.3390/cancers14215468.
Hepatocellular carcinoma (HCC) is a major cause of cancer death worldwide due to its high rates of tumor recurrence and metastasis. Aberrant Wnt/β-catenin signaling has been shown to play a significant role in HCC development, progression and clinical impact on tumor behavior. Accumulating evidence has revealed the critical involvement of Wnt/β-catenin signaling in driving cancer stemness and metabolic reprogramming, which are regarded as emerging cancer hallmarks. In this review, we summarize the regulatory mechanism of Wnt/β-catenin signaling and its role in HCC. Furthermore, we provide an update on the regulatory roles of Wnt/β-catenin signaling in metabolic reprogramming, cancer stemness and drug resistance in HCC. We also provide an update on preclinical and clinical studies targeting Wnt/β-catenin signaling alone or in combination with current therapies for effective cancer therapy. This review provides insights into the current opportunities and challenges of targeting this signaling pathway in HCC.
肝细胞癌（HCC）是全球癌症死亡的主要原因，因其肿瘤复发和转移率高。异常的Wnt/β-连环蛋白信号通路已被证明在HCC的发生、发展以及对肿瘤行为的临床影响中起重要作用。越来越多的证据表明，Wnt/β-连环蛋白信号通路在驱动癌症干性和代谢重编程中起关键作用，而这两者被视为新出现的癌症标志。在本综述中，我们总结了Wnt/β-连环蛋白信号通路的调控机制及其在HCC中的作用。此外，我们还介绍了Wnt/β-连环蛋白信号通路在HCC代谢重编程、癌症干性和耐药性中的调控作用的最新进展。我们还介绍了针对Wnt/β-连环蛋白信号通路单独或与当前疗法联合用于有效癌症治疗的临床前和临床研究的最新进展。本综述深入探讨了在HCC中靶向该信号通路目前面临的机遇和挑战。
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