# Targeting lung and breast cancer cell oxidative metabolism with D-penicillamine and disulfiram

> **NIH NIH F30** · UNIVERSITY OF IOWA · 2020 · $50,520

## Abstract

Project Summary/Abstract:
Lung and breast cancer are two of the most common cancers in the United States with an estimated 224,390
and 246,660 new cases in 2016, respectively. Current treatment regimens for these cancers include extensive
chemotherapy, surgery, and radiation therapy, but despite multiple modalities of treatment, the 5 year survival
for lung cancer is only 17.7%, and the estimated number of deaths from breast cancer in 2016 is 40,450
individuals. Given these outcomes, new treatment options that can selectively kill cancer cells as well as early
progenitor cancer stem cells that are believed to be responsible for development of drug resistance and
metastasis are urgently needed. The repurposing of currently available relatively non-toxic FDA approved
drugs such as D-penicillamine (DPEN) and disulfiram (DSF), which are possibly able to target fundamental
differences in oxidative metabolism in cancer versus normal cells, could provide a promising and rapidly
translatable strategy to target these deadly cancers. Preliminary data generated by the applicant has shown for
the first time that DPEN and DSF are selectively toxic to breast and lung cancer cells, relative to normal breast
and lung epithelial cells, when combined with physiologically relevant non-toxic concentrations of copper, and
this toxicity was dependent on H2O2-mediated oxidative stress. In addition, DPEN and DSF were found to be
capable of enhancing the effects of radiation on lung cancer cells and were able to inhibit the increased
percentage of viable cancer stem cells (as detected by ALDH1 activity) in bulk populations of lung cancer cells
exposed to radiation. These promising preliminary results have led to the overarching hypothesis that: DPEN
and DSF selectively induce cytotoxicity and radio-chemo-sensitization in human breast and lung
cancer cells (versus normal cells) and cancer stem cells via H2O2-mediated oxidative stress that is
mitigated by disruptions in intracellular redox active metal ions. Aim 1 of this proposal will determine in
vitro if DPEN and DSF are differentially cytotoxic to lung and breast cancer cells (versus normal cells) via
H2O2-mediated oxidative stress and disruptions in redox active metal ions. Aim 2 will determine if DPEN and
DSF combined with ionizing radiation and/or standard chemotherapy will selectively (relative to normal cells)
enhance cancer cell cytotoxicity in vitro and in vivo via a mechanism mediated by H2O2, redox active metal
ions, and suppression of cancer stem cell survival. The successful completion of these studies will define
biochemical mechanisms underlying DPEN and DSF selective toxicity in cancer versus normal cells and will
provide new means for exploiting fundamental differences in oxidative metabolism between these cell
populations in order to increase treatment efficacy using traditional cancer therapies. The proposed project will
also allow the applicant to expand her basic science investigational skills, exper...

## Key facts

- **NIH application ID:** 9852299
- **Project number:** 5F30CA213817-04
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Kelly Hubert
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $50,520
- **Award type:** 5
- **Project period:** 2017-03-02 → 2021-03-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9852299

## Citation

> US National Institutes of Health, RePORTER application 9852299, Targeting lung and breast cancer cell oxidative metabolism with D-penicillamine and disulfiram (5F30CA213817-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9852299. Licensed CC0.

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