Metabolic dysregulation and emerging therapeutical targets for hepatocellular carcinoma.
Metabolic dysregulation and emerging therapeutical targets for hepatocellular carcinoma.
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DOI：
10.1016/j.apsb.2021.09.019
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发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Xiong J
中科院分区：
文献类型：
--
作者：
Du D;Liu C;Qin M;Zhang X;Xi T;Yuan S;Hao H;Xiong J
肝细胞癌是一种侵袭性的人类癌症，在全球范围内发病率呈上升趋势。人们已经做出了多种努力来探索治疗肝癌的药物治疗方法，如靶向酪氨酸激酶抑制剂、基于免疫的治疗和联合化疗。然而，目前的策略存在局限性，例如包括化疗耐药性。肿瘤的发生和发展是由代谢的重新编程驱动的，特别是在肝细胞癌的发展过程中。最近，代谢相关脂肪性肝病(MAFLD)是对非酒精性脂肪性肝病(NAFLD)新命名的重新评估，表明代谢在包括肝细胞癌在内的肝病发病机制中的作用日益受到重视，从而为肝细胞癌的治疗提供了靶向代谢异常的新策略。本文重点介绍了适合于肝癌药物干预的葡萄糖、脂肪酸、氨基酸和谷氨酰胺代谢靶点。我们还总结和讨论了目前针对肝细胞癌治疗过程中代谢紊乱的药物和研究。此外，还讨论了以代谢为靶点的肝癌治疗的发现和发展中的机遇和挑战。代谢紊乱在肝细胞癌的发病机制中受到重视，因此靶向代谢紊乱的药物或化学物质被开发为治疗肝细胞癌的潜在药物。
Hepatocellular carcinoma (HCC) is an aggressive human cancer with increasing incidence worldwide. Multiple efforts have been made to explore pharmaceutical therapies to treat HCC, such as targeted tyrosine kinase inhibitors, immune based therapies and combination of chemotherapy. However, limitations exist in current strategies including chemoresistance for instance. Tumor initiation and progression is driven by reprogramming of metabolism, in particular during HCC development. Recently, metabolic associated fatty liver disease (MAFLD), a reappraisal of new nomenclature for non-alcoholic fatty liver disease (NAFLD), indicates growing appreciation of metabolism in the pathogenesis of liver disease, including HCC, thereby suggesting new strategies by targeting abnormal metabolism for HCC treatment. In this review, we introduce directions by highlighting the metabolic targets in glucose, fatty acid, amino acid and glutamine metabolism, which are suitable for HCC pharmaceutical intervention. We also summarize and discuss current pharmaceutical agents and studies targeting deregulated metabolism during HCC treatment. Furthermore, opportunities and challenges in the discovery and development of HCC therapy targeting metabolism are discussed. Metabolic dysregulation is emphasized in the pathogenesis of hepatocellular carcinoma (HCC), thus agents or chemicals are developed as potentials to treat HCC by targeting deregulated metabolism.
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