# Dissecting the role of the immune system in the radiation response of Kras-mutant tumors

> **NIH NIH F30** · DUKE UNIVERSITY · 2020 · $46,300

## Abstract

ABSTRACT:
RAS mutations occur in one-third of all human cancers and confer a poor prognosis with a high risk of
recurrence. Oncogenic KRAS mutations are particularly common among non-small cell lung cancer and
pancreatic cancer, which are frequently treated with radiation therapy. These genetic alterations have been
associated with radiation resistance, which often contributes to therapy failure for these common malignancies.
The underlying mechanism by which KRAS-mediated resistance to ionizing radiation occurs is poorly
understood, but has been proposed to be mediated via a cell-autonomous signaling mechanism. Using
genetically engineered mouse models of primary soft tissue sarcomas, my preliminary data demonstrate that
Kras-mutant tumors respond poorly to radiation compared to Kras wild-type tumors in an immune system-
dependent manner. To understand the role of myeloid cells in the radiation response of Kras-mutant tumors, I
will apply Cre-LoxP technology to generate Kras-mutant and Kras-wild type tumors while manipulating specific
subsets of myeloid cells.
The long-term goal of this project is to elucidate and harness mechanisms of radiation resistance to enhance
the efficacy of radiation therapy in the clinic. The primary objective of this project is to dissect the role of
immune cells in the radiation response of Kras-driven tumors by genetically manipulating myeloid cells. By
improving our understanding of the role of Kras mutations in the immune response to radiation therapy, a
critical mechanism of radiation resistance will be defined. Evaluating the role of the immune system in the
radiation response of primary cancers will help determine the viability of targeting the immune system to
improve the efficacy of radiation therapy in the clinic.

## Key facts

- **NIH application ID:** 9982234
- **Project number:** 5F30CA221268-04
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Amy Jordan Wisdom
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $46,300
- **Award type:** 5
- **Project period:** 2017-07-01 → 2021-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9982234

## Citation

> US National Institutes of Health, RePORTER application 9982234, Dissecting the role of the immune system in the radiation response of Kras-mutant tumors (5F30CA221268-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9982234. Licensed CC0.

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