# Development and Testing of a Novel Biospecific using modified Gemcitibine to target and treat Pancreatic Cancer

> **NIH NIH U54** · FLORIDA AGRICULTURAL AND MECHANICAL UNIV · 2023 · $49,136

## Abstract

ABSTRACT – Pilot Project 5
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive human malignancies and the survival
rate remains stagnant with a 5-year survival rate of only 5-8%. Black/African Americans (B/AA) individuals
experience the highest prevalence and lowest overall survival rates of PDAC compared to their White
counterparts. FOLFIRINOX (5-fluorouracil, leucovorin, oxaliplatin, and irinotecan) is often the preferred
chemotherapy treatment choice for patients with PDAC, but considerable toxicities have limited its use. The
decreased expression of nucleoside transporters due to genetic and epigenetic reasons appeared to account for
Gem resistance. In addition, deoxycytidine kinase (dCK), which is responsible for Gem phosphorylation into the
active form, is postulated to correlate with Gem efficacy. To address these challenges, we have modified Gem
to 4-(N)- stearoylGem (4NSG) to: i) block the CDA attack on Gem, and ii) increase Gem transport into PDAC
cells. Our recent results revealed highly expressed epidermal growth factor receptors (EGFR) in pancreatic
tumor samples. Guided by our recently published and unpublished results, we hypothesize that optimized 4NSG
nanoparticles with surface-modified anti-EGFR antibody (4NSGnpcetu) will improve the therapeutic efficacy of
Gem. We propose the following specific aims to address this hypothesis. Aim 1: Test the efficacy of 4NSGnpcetu,
in B/AA, and White patient-derived organoid models (PDOs) with stroma and in primary PDAC cells. Aim 2:
Evaluate the therapeutic efficacy of 4NSGnpcetu in PDAC PDX mouse models bearing subcutaneous tumors from
B/AA and White patients. Aim 3: Measure dCK RNA/protein expression in PDAC PDX tumor models and SNP
genotypes in PDAC cases and controls in the MultiEthnic dataset. Our studies will determine whether racial
differences in dCK variant, gene expression, and protein activity can correlate with improved Gem efficacy in
B/AA and /or White PDAC patients. The valuable information obtained will significantly advance the overall goal
of improving the response and survival rate in PDAC patients.

## Key facts

- **NIH application ID:** 10762216
- **Project number:** 2U54CA233396-06
- **Recipient organization:** FLORIDA AGRICULTURAL AND MECHANICAL UNIV
- **Principal Investigator:** Edward Kwasi Agyare
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $49,136
- **Award type:** 2
- **Project period:** 2018-09-19 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10762216

## Citation

> US National Institutes of Health, RePORTER application 10762216, Development and Testing of a Novel Biospecific using modified Gemcitibine to target and treat Pancreatic Cancer (2U54CA233396-06). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10762216. Licensed CC0.

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