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Review Article

在肝细胞癌中靶向神经酰胺代谢：治疗干预的新点。

卷 27, 期 39, 2020

页: [6611 - 6627] 页: 17

弟呕挨: 10.2174/0929867326666190911115722

价格: $65

摘要

背景：肝细胞癌（HCC）由于其不受控制的细胞生长和增殖，侵袭性以及遗传的化学抗性，是全球最大的健康负担之一。尽管目前有针对HCC的不同治疗选择，但具有区域性和远期疾病的HCC患者的5年相对存活率仍然较低，这突出表明迫切需要针对HCC的新型治疗策略。最近的发现强烈表明特定的脂质种类，例如鞘脂，在肿瘤发生中起重要作用。 目的：我们将概述神经酰胺代谢在肝癌的发病机理和治疗中的作用的最新文献发现。 结果：HCC的特征是神经酰胺代谢失调，这可能归因于神经酰胺合酶2、4和6，酸性和碱性神经酰胺酶2和3的活性和表达改变，以及鞘氨醇激酶（SphK）1的失调。 2和1鞘氨醇磷酸酯，特别是S1PR1。其中，SphK2已成为HCC的临床相关药物靶标，目前正在针对晚期HCC患者的临床试验中研究其对ABC294640的抑制作用。另一个有希望的策略包括恢复肝癌组织中神经酰胺的水平，其中纳米脂质体神经酰胺，特别是C6-神经酰胺已成为抗肝癌的有效治疗剂，其安全性和推荐剂量目前正在临床研究中。 结论：开发专门针对神经酰胺代谢的新药可以在HCC患者中提供增强的治疗反应和改善的生存结果。

关键词: 肝细胞癌，神经酰胺，1-磷酸鞘氨醇，鞘氨醇激酶，化学耐药性，索拉非尼，5-氟尿嘧啶。

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