The regulation of cellular processes by ion channels has become central to the study of cancer mechanisms. Designing molecules that can modify ion channels specific to tumor cells is a promising area of targeted drug delivery and therapy. Despite their potential in drug discovery, venom peptides – a group of natural products – have largely remained understudied and under-characterized. In general, venom peptides display high specificity and selectivity for target ion channels. Therefore, they may represent an effective strategy for selectively targeting the dysregulation of ion channels in tumor cells. This review examines existing venom peptide therapies for different cancer types and focuses on the application of snail venom peptides in hepatocellular carcinoma (HCC), the most common form of primary liver cancer worldwide. We provide insights into the mode of action of venom peptides that have been shown to target tumors. We also explore the benefit of using new computational methods like de novo protein structure prediction to screen venom peptides and identify potential druggable candidates. Finally, we summarize the role of cell culture, animal, and organoid models in developing effective therapies against HCC and highlight the need for creating models that represent the most disproportionately affected ethnicities in HCC.

中文翻译：

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用毒肽靶向肝脏肿瘤中失调的离子通道

离子通道对细胞过程的调节已成为癌症机制研究的核心。设计可以修饰肿瘤细胞特异性离子通道的分子是靶向药物输送和治疗的一个有前途的领域。尽管毒液肽（一组天然产物）在药物发现方面具有潜力，但在很大程度上仍未得到充分研究和表征。一般来说，毒液肽对目标离子通道表现出高度的特异性和选择性。因此，它们可能代表了选择性靶向肿瘤细胞中离子通道失调的有效策略。本综述研究了针对不同癌症类型的现有毒液肽疗法，并重点关注蜗牛毒液肽在肝细胞癌（HCC）（全球最常见的原发性肝癌）中的应用。我们提供了对毒液肽作用模式的见解，这些肽已被证明可以靶向肿瘤。我们还探索了使用新的计算方法（例如从头蛋白质结构预测）来筛选毒液肽并识别潜在的可药物候选者的好处。最后，我们总结了细胞培养、动物和类器官模型在开发有效的 HCC 疗法中的作用，并强调需要创建代表 HCC 中受影响最严重的种族的模型。