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
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Date
2022
Authors
Burska, Agata N.
Ilyassova, Bayansulu
Dildabek, Aruzhan
Khamijan, Medina
Begimbetova, Dinara
Molnár, Ferdinand
Journal Title
Journal ISSN
Volume Title
Publisher
Cell
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.
Description
Keywords
Type of access: Open Access, Kirsten rat sarcoma (KRAS) mutant ancers, Warburg effect, oxidative stress, arsenic trioxide (ATO), vitamin C (VC also known as ascorbic acid), reactive oxygen species (ROS), suicidal ROS production by mitochondrial (SRPM)
Citation
Burska, A., Ilyassova, B., Dildabek, A., Khamijan, M., Begimbetova, D., Molnár, F., & Sarbassov, D. D. (2022). 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. Cells, 11(21), 3454. https://doi.org/10.3390/cells11213454