Targeting Dysregulated Ion Channels in Liver Tumors with Venom Peptides

Favour Achimba, Bulat Faezov, Brandon Cohen, Roland Dunbrack, Mande Holford

Research output: Contribution to journalReview articlepeer-review

Abstract

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.

Original languageAmerican English
Pages (from-to)139-147
Number of pages9
JournalMolecular Cancer Therapeutics
Volume23
Issue number2
DOIs
StatePublished - Feb 1 2024

Keywords

  • channelopathy
  • hepatocellular carcinoma
  • ion channels
  • liver tumor
  • snail venom
  • teretoxins
  • transient receptor potential ion channels
  • venom peptides
  • Peptides/chemistry
  • Carcinoma, Hepatocellular/drug therapy
  • Animals
  • Ion Channels/metabolism
  • Liver Neoplasms/drug therapy
  • Venoms/pharmacology

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