Auranofin and Pharmacologic Ascorbate as Radiomodulators in the Treatment of Pancreatic Cancer

Garett J Steers; Gloria Y Chen; Brianne R O'Leary; Juan Du; Hannah Van Beek; Joseph J Cullen

doi:10.3390/antiox11050971

Back

Auranofin and Pharmacologic Ascorbate as Radiomodulators in the Treatment of Pancreatic Cancer

Journal article

Open access

Peer reviewed

Auranofin and Pharmacologic Ascorbate as Radiomodulators in the Treatment of Pancreatic Cancer

Garett J Steers, Gloria Y Chen, Brianne R O'Leary, Juan Du, Hannah Van Beek and Joseph J Cullen

Antioxidants, Vol.11(5), p.971

05/14/2022

DOI: 10.3390/antiox11050971

PMCID: PMC9137675

PMID: 35624835

Files and links (1)

url

https://doi.org/10.3390/antiox11050971View

Published (Version of record) Open Access

Abstract

Pancreatic cancer accounts for nearly one fourth of all new cancers worldwide. Little progress in the development of novel or adjuvant therapies has been made over the past few decades and new approaches to the treatment of pancreatic cancer are desperately needed. Pharmacologic ascorbate (P-AscH , high-dose, intravenous vitamin C) is being investigated in clinical trials as an adjunct to standard-of-care chemoradiation treatments. In vitro, P-AscH has been shown to sensitize cancer cells to ionizing radiation in a manner that is dependent on the generation of H O while simultaneously protecting normal tissue from radiation damage. There is renewed interest in Auranofin (Au), an FDA-approved medication utilized in the treatment of rheumatoid arthritis, as an anti-cancer agent. Au inhibits the thioredoxin antioxidant system, thus increasing the overall peroxide burden on cancer cells. In support of current literature demonstrating Au's effectiveness in breast, colon, lung, and ovarian cancer, we offer additional data that demonstrate the effectiveness of Au alone and in combination with P-AscH and ionizing radiation in pancreatic cancer treatment. Combining P-AscH and Au in the treatment of pancreatic cancer may confer multiple mechanisms to increase H O -dependent toxicity amongst cancer cells and provide a promising translatable avenue by which to enhance radiation effectiveness and improve patient outcomes.

peroxiredoxin

pancreatic cancer

pharmacologic ascorbate

thioredoxin

vitamin C

thioredoxin reductase

Auranofin

Details

Title: Subtitle: Auranofin and Pharmacologic Ascorbate as Radiomodulators in the Treatment of Pancreatic Cancer
Creators: Garett J Steers - Roy J. and Lucille A. Carver College of Medicine
Gloria Y Chen - Roy J. and Lucille A. Carver College of Medicine
Brianne R O'Leary - University of Iowa
Juan Du - University of Iowa
Hannah Van Beek - Free Radical and Radiation Biology Program, Department of Radiation Oncology, The University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
Joseph J Cullen - Roy J. and Lucille A. Carver College of Medicine
Resource Type: Journal article
Publication Details: Antioxidants, Vol.11(5), p.971
DOI: 10.3390/antiox11050971
PMID: 35624835
PMCID: PMC9137675
NLM abbreviation: Antioxidants (Basel)
ISSN: 2076-3921
eISSN: 2076-3921
Grant note: P01 CA217797 / NIH HHS T32 CA78586 / NIH HHS T32 CA148062 / NIH HHS
Language: English
Date published: 05/14/2022
Academic Unit: Surgery; Radiation Oncology
Record Identifier: 9984312962502771

Metrics

28 Record Views

9 Times Cited - Web of Science