# Phospholipase D1 and pancreatic cancer

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $403,688

## Abstract

Summary
The long-term goals of this project are to understand the role of phospholipase D1 (PLD1) in
pancreatic ductal adenocarcinoma (PDA) pathogenesis, chemoprevention, and therapeutics.
PDA is a complex and lethal cancer with a five-year survival of <9%. Surgery, which offers the
only realistic hope, has a limited role, whereas current chemotherapy or radiation therapy
regimens offer minimal or no help. Therefore, the magnitude of this problem mandates the search
for new strategies to combat this disease; being the identification of new targets for treatment a
critical component. Phospholipase D1 (PLD1), a lipid-signaling enzyme, has been shown to play
a role in the progression of various types of cancer. For example, PLD1: a) is increased in
abundance or activity in various human cancers; b) is linked with proliferative signaling and
resistance to cell death, and c) promotes tumor growth and metastasis. In addition, PLD1 has
been recently shown to be elevated in clinical samples of pancreatic cancer, and inversely
correlate with patient survival. These findings suggest the potential use of PLD inhibitors as
cancer therapeutics. However, to date, there is a dearth of information regarding the exact role
played by PLD1 in PDA. Preliminary studies in our laboratory have shown in animal models of
pancreatic cancer, that inhibiting PLD1 reduces pancreatic tumor growth, extends survival and
enhances the chemotherapeutic effect of gemcitabine, the most commonly used drug for treating
pancreatic cancer patients. Based on the above, the objective of this R21 proposal is to define
the role of PLD1 in PDA growth. We hypothesize that PLD1 is a key enzyme in PDA growth. We
will employ, biochemical, molecular, and in vivo studies to evaluate this hypothesis and to
advance PLD1 as a novel therapeutic target. We will focus on the following specific aims: 1)
Establish and define the role of phospholipase D1 (PLD1) in regulating PDA progression, by a)
defining the in vivo role of PLD1 in the development of PDA using genetically-engineered mouse
models; and b) determining the cellular roles of PLD1 (both the tumor and the microenvironment)
in regulating cell growth in pancreatic cancer; and 2) Determine the mechanisms underlying the
inhibition of PDA progression by disruption of PLD1. At the completion of these studies, we expect
to have deciphered key functions of PLD1 in pancreatic cancer. These results may allow us to
define and establish PLD1 as a novel and heretofore unappreciated major regulator of pancreatic
cancer progression. Given the importance of PDA and the lack of effective agents against it, we
believe that the proposed work holds the promise of a significant advance in this area.

## Key facts

- **NIH application ID:** 9969912
- **Project number:** 1R21CA227416-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Gerardo Guillermo Mackenzie
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $403,688
- **Award type:** 1
- **Project period:** 2020-09-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9969912

## Citation

> US National Institutes of Health, RePORTER application 9969912, Phospholipase D1 and pancreatic cancer (1R21CA227416-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9969912. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*