# Microbiota pancreas interactions during cancer

> **NIH NIH R21** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2022 · $186,813

## Abstract

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal forms of cancer, with an incidence rate
almost equal to its mortality rate. It has few strongly predictive risk factors, either genetic or environmental, it
most often produces symptoms at advanced, inoperable stages, and it is resistant to both generic and targeted
therapies. PDAC patients have had little benefit from the advances in early detection, prevention and treatment
that have improved care for other common cancers. Intriguingly, however, recent evidence suggests that the
microbial community of the gastrointestinal tract – the gut microbiota – represents a potential source of both
biomarkers and therapeutic targets in PDAC. Published studies, and our own preliminary work, indicate that
the microbiota is required for efficient pancreatic tumor initiation, although the underlying species and
molecular mechanisms remain unknown. In addition, the microbiota of human PDAC patients is distinct from
healthy controls, and early microbial alterations represent risk factors for later cancer development. Again, the
mechanistic basis for this relationship is unknown, as it is a challenge to establish cause-and-effect
relationships through observational studies, or through the use of conventional mouse models that lack control
over the timing of tumor-initiating events. We hypothesize that the microbiota harbors a diverse array of
cancer-promoting and -inhibiting species, acting at multiple times and through multiple mechanisms including
modulation of immune responses, and that inter-individual heterogeneity in these species contributes to PDAC
risk and disease outcome. To test this hypothesis, and to identify components of the microbiota as predictive
markers of disease and targets for prevention and treatment, we propose to establish an experimental platform
for functional analysis of the microbiota, based on a temporally-inducible mouse model of endogenous PDAC
initiation and progression. We will use orthogonal analyses of time-specific and antibiotic-specific microbial
ablation to dissect the roles of the endogenous mouse microbiota (Aim 1), and establish mice with “humanized”
microbiota from individual PDAC patients and healthy controls to characterize the effects of disease-specific
microbial communities on tumorigenesis and anti-tumor immunity (Aim 2). Our work will directly identify
relevant members of the microbiota that contribute functionally to pancreatic cancer risk, and provide the
knowledge base to develop microbial biomarkers and therapies to mitigate cancer progression.

## Key facts

- **NIH application ID:** 10474561
- **Project number:** 5R21CA253673-02
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Lewis C Murtaugh
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $186,813
- **Award type:** 5
- **Project period:** 2021-09-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10474561

## Citation

> US National Institutes of Health, RePORTER application 10474561, Microbiota pancreas interactions during cancer (5R21CA253673-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10474561. Licensed CC0.

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