# Targeting apoptotic caspases to enhance cancer radiotherapy

> **NIH NIH R01** · DUKE UNIVERSITY · 2021 · $467,757

## Abstract

PROJECT SUMMARY
The basis for the success of radiation therapy is long believed to be direct killing and elimination of
cancer cells. Therefore, most previous research efforts have focused on enhancing the direct killing
effects of radiotherapy. However, recently, it was realized that the host immune system plays key
roles in determining the treatment outcome of cytotoxic cancer therapy. In many instances, it has been
shown that radiation therapy can activate the immune system to attack cancer cells. However, the
molecular mechanisms involved in radiation-induced immune cell activation are poorly understood.
In the current project, we intend to test the hypothesis that blockade of certain apoptotic caspases
will enhance the efficacy of radiotherapy and immune checkpoint inhibitors by increasing
immunogenic cell death. Our hypothesis is based on both published data on the immune-stimulatory
effect of radiotherapy and our preliminary data demonstrating strong immunogenic effects of blocking
apoptotic caspases.
To test our hypothesis, we will attempt to dissect the roles of individual caspases by use of murine
tumor cells with CRISPR-Cas9 mediated genetic knockout and evaluating their response to
radiotherapy in vitro and in mice (Aim 1). We will then try to identify downstream factors of caspases
that are important in radiation induced immunogenic cell death (Aim 2). Finally, we will evaluate if
inhibition of caspases is a feasible strategy to enhance radiotherapy in combination with immune-
checkpoint inhibitor therapy (Aim 3).
Upon completion of our proposed project, we hope to establish the biological roles of apoptotic
caspases in immunogenic cell death during radiotherapy and lay the foundation for evaluating caspase
inhibitors as potential agents to enhance radiotherapy and immuno-checkpoint inhibitor therapy in
human patients.

## Key facts

- **NIH application ID:** 10064085
- **Project number:** 5R01CA216876-04
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Chuan-Yuan Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $467,757
- **Award type:** 5
- **Project period:** 2017-12-05 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10064085

## Citation

> US National Institutes of Health, RePORTER application 10064085, Targeting apoptotic caspases to enhance cancer radiotherapy (5R01CA216876-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10064085. Licensed CC0.

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