# Repurposing redox active agents for exploiting differences in cancer cell metabolism for improving cancer therapy

> **NIH NIH R50** · UNIVERSITY OF IOWA · 2021 · $155,127

## Abstract

Abstract
Dr. Melissa Fath is currently 100% supported by the program project grant entitled “Exploiting Redox
Metabolism Using Pharmacological Ascorbate (P-AscH−) for Cancer Therapy” (P01 CA217797). The theme of
this P01 is exploiting cancer cell redox metabolism using pharmacological ascorbate (P-AscH-; high dose
intravenous vitamin C) for improving cancer therapy. The P01 is composed of 3 major research projects and 3
core facilities. The proposal is highly integrated and focused on preclinical, translational and clinical studies
relevant to the use of P-AscH− in cancer therapy and Dr. Fath's research will impact all three of the research
projects and two of the cores. This R50 application proposes 100 % salary support for Dr. Fath to support all
the projects and two cores in the P01 research program as well as any new research initiatives funded by NCI
that may arise from that work. The Unit Director of the current proposal, Dr. Douglas Spitz, is part of the multi-
PI leadership team as well as the principle investigator on Project 2, “Exploiting Labile Iron Pools for Improving
NSCLC Therapy Using Pharmacological Ascorbate”. Specifically Project 2 in the P01 will test the hypothesis
that P-AscH− selectively sensitizes non-small cell lung cancers to radiation and chemotherapy by selectively
increasing cancer cell steady-state levels of H2O2 as a result of specific disruptions in redox-active iron
metabolism mediated by endogenous levels of O2.-/H2O2 . The Free Radical and Radiation Biology Program
(FRRBP) in the Department of Radiation Oncology at the University of Iowa is an ideal scientific environment
for this proposed research because of its historic roots in radiation biology as well as the free radical theory of
cancer in association with a strong Radiation Oncology Department. Dr. Spitz is the division director of FRRBP
and Dr. Fath is an associate research scientist that has been an active collaborative member for over 10 years.
Dr. Fath has considerable expertise in testing the involvement of free radicals, thiol oxidation, redox sensitive
signaling pathways, and oxidative damage end-points in many studies exploiting manipulations of redox
metabolism to repurpose drugs for cancer therapy. Her background and training in Clinical Pharmacy,
Medicinal & Natural Products Chemistry, and Free Radical Cancer Biology make her ideally suited to work in
this highly collaborative and integrated group doing both in vitro and in vivo translational research as well as
supporting clinical trials. Dr. Fath will focus on the redox biology of O2·- and H2O2 as well as the involvement of
Fe metabolism in the differential effects of that mediate P-AscH- induced radio-chemotherapy sensitization.
She will quantify radio-chemo- sensitization, measure steady-state H2O2, study and manipulate labile iron
pools using both pharmacological and genetic approaches, and assess oxidative stress, and DNA damage
endpoints in cancer treatment models. In addition, Dr. Fath ...

## Key facts

- **NIH application ID:** 10239057
- **Project number:** 5R50CA243693-03
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Melissa Ann Fath
- **Activity code:** R50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $155,127
- **Award type:** 5
- **Project period:** 2019-09-17 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10239057

## Citation

> US National Institutes of Health, RePORTER application 10239057, Repurposing redox active agents for exploiting differences in cancer cell metabolism for improving cancer therapy (5R50CA243693-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10239057. Licensed CC0.

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