Enhancing an Oxidative "Trojan Horse" Action of Vitamin C with Arsenic Trioxide for Effective Suppression of KRAS-Mutant Cancers: A Promising Path at the Bedside

Agata N Burska, Bayansulu Ilyassova, Aruzhan Dildabek, Medina Khamijan, Dinara Begimbetova, Ferdinand Molnár, Dos D Sarbassov

Research output: Contribution to journalReview articlepeer-review

1 Citation (Scopus)

Abstract

The turn-on mutations of the KRAS gene, coding a small GTPase coupling growth factor signaling, are contributing to nearly 25% of all human cancers, leading to highly malignant tumors with poor outcomes. Targeting of oncogenic KRAS remains a most challenging task in oncology. Recently, the specific G12C mutant KRAS inhibitors have been developed but with a limited clinical outcome because they acquire drug resistance. Alternatively, exploiting a metabolic breach of KRAS-mutant cancer cells related to a glucose-dependent sensitivity to oxidative stress is becoming a promising indirect cancer targeting approach. Here, we discuss the use of a vitamin C (VC) acting in high dose as an oxidative "Trojan horse" agent for KRAS-mutant cancer cells that can be potentiated with another oxidizing drug arsenic trioxide (ATO) to obtain a potent and selective cytotoxic impact. Moreover, we outline the advantages of VC's non-natural enantiomer, D-VC, because of its distinctive pharmacokinetics and lower toxicity. Thus, the D-VC and ATO combination shows a promising path to treat KRAS-mutant cancers in clinical settings.

Original languageEnglish
JournalCells
Volume11
Issue number21
DOIs
Publication statusPublished - Nov 1 2022

Keywords

  • Humans
  • Arsenic Trioxide/pharmacology
  • Ascorbic Acid/pharmacology
  • Proto-Oncogene Proteins p21(ras)/genetics
  • Reactive Oxygen Species/metabolism
  • Cell Line, Tumor
  • Oxidative Stress
  • Vitamins/pharmacology
  • Oxidation-Reduction
  • Neoplasms/drug therapy

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