# Tumor-intrinsic and paracrine roles of endoglin in pancreatic cancer

> **NIH NIH R01** · UNIVERSITY OF ARIZONA · 2024 · $357,480

## Abstract

ABSTRACT
Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy featuring early metastasis, late onset of
symptoms, and notorious resistance to existing therapies. A critically elusive aspect of this disease relates to
the tumors which are often hypovascularized relative to other solid cancers, manifesting in poor perfusion and
impaired drug delivery. In preliminary studies, we discovered that endoglin, normally an endothelial-specific
TGF-beta coreceptor required for angiogenesis, is expressed as two variants in pancreatic cancer cells- the
wildtype, which supports tumor-intrinsic growth and chemoresistance; and a novel splice variant with distinct
structural features that gets secreted to inhibit tumor vascularization. To understand their interplay in the
tumor microenvironment, we have generated a variety of cellular and pharmacologic reagents to interrogate
the underlying mechanisms and their therapeutic potential. We propose to define novel paracrine
mechanisms of TGF-beta signaling that suppress PDAC vascularization (Aim 1); and identify tumor-intrinsic
endoglin pathways as critical therapeutic targets in PDAC (Aim 2); and determine the endoglin variants as
distinct spatiotemporal targets during disease progression (Aim 3). Results from these studies will define TGF-
beta-based mechanisms critical for PDAC tumor growth and vascularization and deliver clinically relevant
data for improved patient-based therapeutics.

## Key facts

- **NIH application ID:** 10895427
- **Project number:** 5R01CA275036-02
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Nam Y Lee
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $357,480
- **Award type:** 5
- **Project period:** 2023-08-01 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10895427

## Citation

> US National Institutes of Health, RePORTER application 10895427, Tumor-intrinsic and paracrine roles of endoglin in pancreatic cancer (5R01CA275036-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10895427. Licensed CC0.

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