# Impact of the Microbiome on  the Efficacy of Radiation Therapy

> **NIH NIH R01** · CEDARS-SINAI MEDICAL CENTER · 2021 · $350,000

## Abstract

PROJECT SUMMARY
Breast cancer remains the most common cancer in North America and the second leading cause of cancer death
in women. Radiation therapy (RT) plays an integral part in the treatment of breast cancer with more than half of
all breast cancer patients receiving radiation sometime during the course of their treatment. The conventional
view of RT has largely focused on the effect of RT on the tumor cells themselves. However, recent studies have
demonstrated a critical role for the immune system in determining the response of tumors to RT. Further, multiple
studies have identified the bacterial and fungal microbiomes as key regulators of systemic immune responses
in various in states of inflammation including post-chemotherapy immunogenic cell death and asthma
respectively. The microbiome consists of trillions of organisms and a multitude of different species that can
either support or suppress an ongoing immune response and our preliminary data suggests that targeting
intestinal bacteria reduces the efficacy of RT whereas targeting gut fungi can enhance the efficacy of RT. The
objective of this research proposal is to address the mechanism(s) by which intestinal bacteria and fungi shape
the response to RT. The proposal tests the hypothesis that the composition of the bacterial and fungal
microbiome regulates RT-induced immune responses and that the efficacy of RT can be enhanced in vivo by
targeting specific species with the fungal microbiome. To evaluate this hypothesis, the following Aims are
proposed: Aim 1: Characterize the effect of antibiotic- or antifungal-induced intestinal dysbiosis on the efficacy
of radiation and chemotherapy; Aim 2: Define immune mechanism(s) of bacterial and fungal microbiota
regulation of tumor responses to RT; and Aim 3: Examine the role of specific intestinal fungi in modulating the
efficacy of RT. We will accomplish these aims using focal RT delivered with an advanced small animal irradiator
in a murine model of breast cancer and studying the effects of RT in the setting of bacterial or fungal dysbiosis
using a combination of flow cytometry, immunohistochemistry, quantitative PCR and ELISA to determine the
changes in the immune profile of tumors. We will also determine the role of specific fungal species in mediating
the RT-mediated anti-tumor immune response. The significance of this research is that it will provide insights
into the tumor immune responses to radiation that may lead to new microbiome-based therapies for the treatment
of breast cancer and the multiple other solid tumors in which RT plays an integral therapeutic role.

## Key facts

- **NIH application ID:** 10241486
- **Project number:** 5R01CA220000-05
- **Recipient organization:** CEDARS-SINAI MEDICAL CENTER
- **Principal Investigator:** Stephen L. Shiao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $350,000
- **Award type:** 5
- **Project period:** 2017-09-08 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10241486

## Citation

> US National Institutes of Health, RePORTER application 10241486, Impact of the Microbiome on  the Efficacy of Radiation Therapy (5R01CA220000-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10241486. Licensed CC0.

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