# Project 2-Identifying and exploiting metabolic vulnerabilities in PDAC

> **NIH NIH P01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2024 · $650,399

## Abstract

Project 2 -­ Abstract/Summary 
 
Our mechanistic work has established general principles of metabolic reprogramming in PDAC, revealing 
therapeutic insights that show dramatic effects in preclinical models (alanine metabolism blockade) as well as 
benefit in the clinic (autophagy inhibition). In this next cycle, we seek to address two key questions to enable us 
to most effectively define and exploit metabolic vulnerabilities in PDAC. First, how do the different concurrent 
cancer gene mutations that define PDAC subsets influence cancer cell metabolism and the metabolic interplay 
with the TME? Secondly, what role does regulation of mitochondria, organelles central to integration of 
metabolism and innate immune signals, play in metabolic reprogramming and cancer-­stroma cell interactions in 
genetic subsets of Kras* PDAC? By developing a series of novel GEM models and patient-­derived KRAS* PDAC 
models representing major genotypes, we have identified pronounced genetically-­driven differences in tumor 
cell metabolism and cancer-­immune cell interactions. We hypothesize that cooperating genetic alterations drive 
distinct metabolic programs and associated vulnerabilities in cancer cells. Moreover, we predict that immune 
differences will further influence cancer cell metabolism in these distinct genetic settings. To address these 
hypotheses, we propose the following aims: #1 Determine the influence of major PDAC gene mutations on 
metabolic programs;? #2 Assess role of the autophagy/lysosome system on tumor-­TME crosstalk in genetic 
subsets of PDAC;? and, #3 Investigate mitochondrial regulation and relationship to metabolism and inflammatory 
signaling in PDAC subsets.

## Key facts

- **NIH application ID:** 10829379
- **Project number:** 5P01CA117969-19
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** NABEEL El-BARDEESY
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $650,399
- **Award type:** 5
- **Project period:** 2005-12-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10829379

## Citation

> US National Institutes of Health, RePORTER application 10829379, Project 2-Identifying and exploiting metabolic vulnerabilities in PDAC (5P01CA117969-19). Retrieved via AI Analytics 2026-06-02 from https://api.ai-analytics.org/grant/nih/10829379. Licensed CC0.

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