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Updated: Aug 14, 2025

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The Oxidative Drug Combination for Suppressing KRAS G12D Inducible Tumour Growth

Dinara Begimbetova1, Assiya Kukanova1,2, Fatima Fazyl1

  • 1National Laboratory Astana, Nazarbayev University, Astana, Kazakhstan.

Biomed Research International
|January 9, 2023
PubMed
Abstract

Insights

This study shows that combining arsenic trioxide (ATO) with D-ascorbic acid isomer (D-VC) effectively suppresses pancreatic ductal adenocarcinoma (PDAC) in mice. This novel combination offers a promising strategy for treating KRAS mutant cancers.

Area of Science:

  • Oncology
  • Cancer Biology
  • Drug Discovery

Background:

  • Kirsten rat sarcoma (KRAS) protein is crucial in pancreatic ductal adenocarcinoma (PDAC) development.
  • KRAS G12D and G12V mutations present significant challenges in cancer therapy due to treatment resistance.

Purpose of the Study:

  • To evaluate the efficacy of a novel combination of arsenic trioxide (ATO) and D-ascorbic acid isomer (D-VC) in suppressing PDAC.
  • To explore the potential of ATO/D-VC in treating KRAS-mutant cancers by inducing oxidative stress.

Main Methods:

  • The study utilized mouse xenograft models, specifically AK192 cells transplanted into mice.
  • Previous research indicates Vitamin C (VC) selectively targets KRAS-expressing cells at high concentrations.

Main Results:

  • Combining a low dose of ATO with D-VC enhanced the therapeutic effect against PDAC.
  • The combined treatment demonstrated improved efficacy and selectivity compared to individual agents.

Conclusions:

  • The ATO/D-VC combination shows promise as a therapeutic strategy for KRAS-mutant PDAC.
  • This approach may help overcome limitations in drug selectivity and efficacy for challenging cancer types.

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