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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

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...

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Autores principales: Burska, Agata N., Ilyassova, Bayansulu, Dildabek, Aruzhan, Khamijan, Medina, Begimbetova, Dinara, Molnár, Ferdinand, Sarbassov, Dos D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9657932/
https://www.ncbi.nlm.nih.gov/pubmed/36359850
http://dx.doi.org/10.3390/cells11213454
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author Burska, Agata N.
Ilyassova, Bayansulu
Dildabek, Aruzhan
Khamijan, Medina
Begimbetova, Dinara
Molnár, Ferdinand
Sarbassov, Dos D.
author_facet Burska, Agata N.
Ilyassova, Bayansulu
Dildabek, Aruzhan
Khamijan, Medina
Begimbetova, Dinara
Molnár, Ferdinand
Sarbassov, Dos D.
author_sort Burska, Agata N.
collection PubMed
description 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.
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spelling pubmed-96579322022-11-15 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 Burska, Agata N. Ilyassova, Bayansulu Dildabek, Aruzhan Khamijan, Medina Begimbetova, Dinara Molnár, Ferdinand Sarbassov, Dos D. Cells Review 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. MDPI 2022-11-01 /pmc/articles/PMC9657932/ /pubmed/36359850 http://dx.doi.org/10.3390/cells11213454 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Burska, Agata N.
Ilyassova, Bayansulu
Dildabek, Aruzhan
Khamijan, Medina
Begimbetova, Dinara
Molnár, Ferdinand
Sarbassov, Dos D.
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9657932/
https://www.ncbi.nlm.nih.gov/pubmed/36359850
http://dx.doi.org/10.3390/cells11213454
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