# Combination of tumor targeted therapy with stroma modulating agent for PDAC

> **NIH NIH R16** · ST. JOHN'S UNIVERSITY · 2024 · $93,548

## Abstract

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related mortality in the
US (2023) with the 5-year survival rate standing only at less than 9%. Three major issues in pancreatic
tumor treatment are; poor availability of anticancer molecules due to limited blood supply to pancreas,
development of resistance to first line agents e.g. gemcitabine and extensive fibrosis in tumor stroma.
There is an urgent need for a novel and effective therapeutic strategy for PDAC via simultaneously
targeting tumor and its microenvironment. Given the central role of Myc as a mediator of multiple cell
proliferation and survival pathways, it is very essential to target the proto-oncogenic expression of Myc
and controlling K-Ras mediated drug resistance in pancreatic cancer. BRD4 Proteolysis Targeting
Chimera (PROTAC) is an effective way to silence BRD4 and Myc. On another side, collagen type I
dense extracellular matrix of solid tumor severely restricts the uptake of drug, monoclonal antibodies
and nanotherapeutics within pancreatic tumor. Overexpressed focal adhesion kinase (FAK) in
pancreatic cancer plays role in angiogenesis, fibrosis and metastasis. Secreted protein acidic and rich
in cysteine (SPARC) and KRAS mutation collectively facilitate the uptake of albumin into stroma and
PDAC cell, respectively. Based on our promising preliminary results, the parent NIH R16 award was
proposed to explore the albuminosomes for pancreatic tumor specific delivery of BRD4 PROTAC with
simultaneous compromising the fibrotic stoma using FAK inhibitor-PND 1186. The requested grant
supplemental equipment – ECHO Revolution hybrid fluorescence microscope will be of great help in
investigating the cellular uptake mechanism of albuminosomes in 2D and 3D cell culture of pancreatic
cells. The uptake of nanoparticles in tumor stroma and cancer cells is essential for enhancing its
anticancer efficacy. High resolution microscope with automated scanning capability will be useful in (a)
identifying and locating the nanoparticles within PDAC stroma and KRAS mutant PDAC cancer cells
(b) Penetration and anticancer efficacy evaluation using multicellular 3D spheroids of PDAC cell and
cancer associate fibroblasts. The microscope will be housed in the PI’s laboratory. Undergraduate and
graduate students including URM students will use it routinely.

## Key facts

- **NIH application ID:** 11035932
- **Project number:** 3R16GM145556-02S1
- **Recipient organization:** ST. JOHN'S UNIVERSITY
- **Principal Investigator:** Ketankumar D. Patel
- **Activity code:** R16 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $93,548
- **Award type:** 3
- **Project period:** 2023-06-12 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11035932

## Citation

> US National Institutes of Health, RePORTER application 11035932, Combination of tumor targeted therapy with stroma modulating agent for PDAC (3R16GM145556-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11035932. Licensed CC0.

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