# Necroptotic genes in cancer cellular response to radiation

> **NIH NIH R01** · DUKE UNIVERSITY · 2020 · $443,001

## Abstract

Necrosis has long been recognized as a major form of cell death after cellular exposure to
radiation. Necrosis is generally thought to be a passive form of cell death caused by exposure to
stress that leads to initial swelling and eventual rupturing of cellular membrane. Thus it is
traditionally considered to be an unregulated form of cell death, in contrast to apoptosis, where
a defined cascade of molecular events leads to programmed cell death. The discovery of
necroptosis, which involves the systematic activation of select molecular factors that leads to
active permeabilization of cellular membrane, indicates that necrosis could be actively
regulated, similar to apoptosis. However, despite a recent surge of studies on the molecular
signaling events involved in necroptosis, its role in cancer radiotherapy remains unclear.
In this project, we propose to examine in the counter-intuitive hypothesis that the necroptotic
factors play key roles in sustaining tumor growth and mediating tumor resistance to
radiotherapy. Our hypothesis is based on recent results in our laboratory that indicated genetic
deficiencies in necroptotic genes led to weakened tumorigenic abilities and increased radiation
sensitivities of cancer cells. We will use state-of-the-art genome editing technologies such as
CRISPR to examine the role of the necriptotic genes in tumor growth and tumor resistance to
radiotherapy (Aim 1). We will also conduct studies to unveil the mechanisms through which the
necroptotic factors promote tumor growth and tumor resistance to radiation (Aim 2). Finally, we
will evaluate the anti-tumor efficacy of the small molecule inhibitors of the necroptotic factors
alone or in combination with radiotherapy (Aim 3). Upon completion of the project, we hope to
obtain a clearer picture of the role of necroptotic factors in tumor growth and tumor response to
radiation therapy.

## Key facts

- **NIH application ID:** 9878065
- **Project number:** 5R01CA208852-04
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Chuan-Yuan Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $443,001
- **Award type:** 5
- **Project period:** 2017-03-13 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9878065

## Citation

> US National Institutes of Health, RePORTER application 9878065, Necroptotic genes in cancer cellular response to radiation (5R01CA208852-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9878065. Licensed CC0.

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