# Identify tumor suppressor driver genes of pancreatic ductal adenocarcinoma

> **NIH NIH R21** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2020 · $215,985

## Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the most deadly common cancer with no early detection
methods or effective treatments. Understanding the pathological progression and molecular mechanisms
of this disease is crucial to develop new methods for early diagnosis and treatment of PDAC. No
effective drugs are developed to target the most frequently mutated four genes in PDAC, KRAS,
CDKN2A/p16, TP53 and SMAD4. Thus, identifying other PDAC driver genes is crucial for developing
therapeutic targets and studying drug resistance. We have established a platform to sort and culture
normal pancreatic acinar and ductal cells from human donor and demonstrated that we are able to
engineer these cells with oncogenic KRAS and inactivation of p16, TP53, and SMAD4 to generate
invasive PDAC in a xenograft mouse model. Our previous data showed that oncogenic KRAS alone is
not able to generate tumors, suggesting that additional driver mutation(s) are required for tumorigenesis.
In this proposed project, we will employ our unprecedented model as well as a gene editing technique to
screen ~200 potential tumor suppressor driver genes in PDAC to identify the driver mutations that
contribute to the initiation and progression of PDAC. We will use these genetically engineered human
cells to investigate how the driver mutations could affect drug sensitivity in these cells. To achieve our
research goals, two specific aims are proposed: Aim 1. to Identify tumor suppressor genes that can
promote acinar cells to tumors; Aim 2. to assess the therapeutic profile of the engineered acinar and
ductal derived cells. Our model of using genetically engineered normal human acinar cells represents
one of the best models to recapitulate the progression of PDAC in human cells, and thus will lead to
successful identification of PDAC driver mutations, a key step towards better understanding tumor
biology and development of targeted therapies, especially for precision oncology. Our overall goal is to
elucidate the molecular mechanisms which may lead to the development of new diagnostic and
treatment methods for PDAC that can increase survival and improve patient outcomes.

## Key facts

- **NIH application ID:** 9877016
- **Project number:** 1R21CA245437-01
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** Pei Wang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $215,985
- **Award type:** 1
- **Project period:** 2020-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9877016

## Citation

> US National Institutes of Health, RePORTER application 9877016, Identify tumor suppressor driver genes of pancreatic ductal adenocarcinoma (1R21CA245437-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9877016. Licensed CC0.

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