# A phase 0 pilot study to determine if papaverine increases oxygenation in spontaneous canine soft tissue sarcoma

> **NIH NIH R21** · OHIO STATE UNIVERSITY · 2021 · $169,650

## Abstract

ABSTRACT
Tumor hypoxia reduces the effectiveness of radiotherapy by reducing the effective dose delivered to the tumor.
Cells that are severely hypoxic require 2.8-fold greater dose to achieve the same cell kill as those that are fully
oxygenated. For this reason, many groups have tried to deliver more oxygen to tumors as a therapy to reduce
hypoxia and increase radiosensitivity. These strategies did effectively radiosensitize model tumors in rodents,
but did not prove successful in human trials. We have looked at tumor oxygenation differently from the biological
perspective and the evaluation of success perspective. In terms of biology, if we could clinically reduce oxygen
demand rather than increase its supply, we could effectively reduce hypoxia and produce tumor
radiosensitization. We have identified papaverine as an FDA-approved molecule with the ability to inhibit
mitochondrial function at clinical doses. Studies in mouse tumors support the idea that papaverine can
radiosensitize through regulation of oxygen consumption, producing “Metabolic Radiosensitization”. In terms of
the evaluation of papaverine, we propose to test its potential as a clinical radiosensitizer in a heterogeneous
population of spontaneous canine soft tissue sarcomas being treated at OSU Veterinary Medical School. The
heterogeneous host- and tumor genetics generate a clinical trial that we hypothesize will be much more predictive
of human success than a rodent study. Papaverine is not targeted to a specific cancer mutation, and should be
effective as a radiosensitizer in any solid tumor where hypoxia exists. The proposed study will be a phase 0
pharmacodynamics study that will determine if papaverine can increase oxygenation in canine soft tissue
sarcoma as measured by near infrared spectroscopy (FD-NIRS) technology in real time. We propose to test 10
animals with 1 mg/kg and 10 animals with 2 mg/kg papaverine. Correlative biological studies will determine if
baseline tumor hypoxia or other biological variables can predict response to papaverine. These studies will
determine if canine soft tissue sarcoma is a feasible system to test new hypoxic tumor radiosensitizers, and if
papaverine should be considered as a potential radiosensitizer in future interventional trials.

## Key facts

- **NIH application ID:** 9985010
- **Project number:** 5R21CA226477-02
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Nicholas C. Denko
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $169,650
- **Award type:** 5
- **Project period:** 2019-08-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9985010

## Citation

> US National Institutes of Health, RePORTER application 9985010, A phase 0 pilot study to determine if papaverine increases oxygenation in spontaneous canine soft tissue sarcoma (5R21CA226477-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9985010. Licensed CC0.

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