# Understanding the effects of dietary interventions on pancreatic ductal adenocarcinoma therapy cancer

> **NIH NIH R00** · VAN ANDEL RESEARCH INSTITUTE · 2024 · $160,745

## Abstract

Project Summary/Abstract
 Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with limited treatment options
that has a five-year survival rate of <10%. PDAC progression is associated with dysregulated tumor and whole-
body metabolism that impacts therapy and quality of life, which has motivated research on how to best exploit
metabolic dependencies in PDAC for better cancer treatment. Nutrient utilization by cancer cells is regulated in
part by the availability of metabolites in the environment, and the PDAC tumor microenvironment in particular is
highly desmoplastic, consisting of stromal cells, extracellular matrix, and nutrient-poor interstitial fluid. These
microenvironmental factors can impact therapy response, suggesting that the efficacies of metabolism-targeted
drugs can be improved by manipulating components of the PDAC tumor microenvironment. One determinant of
metabolite levels in the tumor microenvironment is diet, and how diet affects cancer progression and treatment
is an important question for many patients. Since dietary recommendations to patients must be made in the
context of therapies being received, the value of any dietary intervention likely lies in its ability to enhance tumor
responses to cancer therapies. Understanding the molecular mechanisms that drive synergistic interactions
between diet and cancer therapies is critical for the translation of dietary recommendations into patient care.
 The main objective of this proposal is to identify dietary interventions that synergize with cancer therapies
to impair PDAC progression. Mouse PDAC models will be used to examine how different diets enhance the
efficacies of standard-of-care FOLFIRINOX chemotherapy (Aim 1), lipid metabolism inhibitors in development
for cancer treatment (Aim 2), and inducers of ferroptosis, a non-apoptotic form of cell death being explored for
PDAC treatment (Aim 3). Mass spectrometry-based metabolomics and lipidomics, stable isotope nutrient tracing,
and RNA sequencing will be used to determine how diet-mediated changes to nutrient levels in the tumor
microenvironment alter the metabolism of PDAC tumors to shape their responses to these therapies. Elucidating
the metabolic mechanisms that underlie synergistic diet-drug combinations will provide scientific evidence that
can benefit patients with guidance on how to best incorporate diet and nutrition into cancer therapy.
 The proposed training plan will help me transition into an independent academic position. A team of
outstanding scientists will mentor me to help me achieve this goal: Dr. Tyler Jacks, a leader in mouse cancer
models; Dr. Omer Yilmaz, a leader in dietary effects on cancer progression; Dr. Caroline Lewis, a leader in mass
spectrometry-based metabolomics and lipidomics technologies; and Dr. Brian Wolpin, a leader in PDAC
epidemiology. My training plan also outlines activities that will help me cultivate mentors, improve my scientific
skillset, improve science communic...

## Key facts

- **NIH application ID:** 10918267
- **Project number:** 5R00CA255928-04
- **Recipient organization:** VAN ANDEL RESEARCH INSTITUTE
- **Principal Investigator:** Evan Chen Lien
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $160,745
- **Award type:** 5
- **Project period:** 2022-04-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10918267

## Citation

> US National Institutes of Health, RePORTER application 10918267, Understanding the effects of dietary interventions on pancreatic ductal adenocarcinoma therapy cancer (5R00CA255928-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10918267. Licensed CC0.

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