# Normalizing PDAC stroma with PCBP2 siRNA nanoparticles to improve the antitumor activity of chemotherapy and immunotherapy

> **NIH NIH R01** · UNIVERSITY OF MISSOURI KANSAS CITY · 2024 · $349,193

## Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related
mortality in the world. Desmoplasia is the most prominent characteristic of PDAC and comprises
up to 80% of the tumor mass. Desmoplasia plays important roles in tumorigenesis and
aggressiveness by promoting the proliferation and metastasis of tumor cells, enhancing
angiogenesis, impeding drug penetration, and contributing to immune evasion. However, clinical
trials employing strategies to deplete PDAC stroma have failed. The stroma acts not only as a
barrier to the penetration of drug and effector T cells, but also as a barrier to restrain the
metastasis of PDAC tumors. Complete depletion of the stroma, therefore, leads to a more
aggressive tumor and a poor survival rate. By contrast, normalization, instead of depletion, of the
stroma in combination with chemotherapy or immunotherapy to kill tumor cells within the stromal
microenvironment is a promising strategy for PDAC therapy.
 In the stromal microenvironment, activated pancreatic stellate cells (PSCs) transform from a
quiescent state into a myofibroblast-like phenotype and express a large amount of extracellular
matrix (ECM). Type I collagen proteins are the main component of the ECM and are responsible
for the major desmoplastic reaction. High levels of type I collagen are associated with a low
survival rate for patients with PDAC. Type I collagen promotes the proliferation and migration of
PDAC cells and inhibits apoptotic cells by binding to integrin.
 We discovered that silencing the poly(rC)-binding protein 2 (αCP2) with siRNA reverses the
accumulation of type I collagen in activated PSCs. Our central hypothesis is that silencing αCP2
modulates the PDAC stroma, thus improving the therapeutic index of chemotherapy and
immunotherapy. The long-term goal of the project is to develop a combination therapy strategy to
treat PDAC.

## Key facts

- **NIH application ID:** 10811672
- **Project number:** 5R01CA271592-02
- **Recipient organization:** UNIVERSITY OF MISSOURI KANSAS CITY
- **Principal Investigator:** Kun Cheng
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $349,193
- **Award type:** 5
- **Project period:** 2023-04-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10811672

## Citation

> US National Institutes of Health, RePORTER application 10811672, Normalizing PDAC stroma with PCBP2 siRNA nanoparticles to improve the antitumor activity of chemotherapy and immunotherapy (5R01CA271592-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10811672. Licensed CC0.

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