# Project 3 – Stromal derived IL-6/STAT3 signaling in the development and progression of PDAC

> **NIH NIH P01** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2024 · $475,342

## Abstract

PROJECT SUMMARY: PROJECT 3
PDAC is among the most deadly malignant solid tumors, with approximately 92% of patients succumbing to the
disease within five years of diagnosis, and with no effective therapies beyond surgery. Importantly, it is widely
recognized that patients with PDAC are especially prone to cachexia, a syndrome characterized by pronounced
weight loss due to depleting skeletal muscle and adipose tissues. As a result, patients are often weak and
fatigued, which makes them less tolerant to chemo- and radiotherapy. The histopathological hallmark of PDAC
is its uniquely dense stromal reaction, comprised of activated, cancer associated fibroblasts, increased extra-
cellular matrix (ECM), immune cell infiltrates, and abnormal angiogenesis. This has engendered attention for
selectively targeting the tumor stroma to increase therapeutic efficacy. However, stromal cancer-associated
fibroblasts can also have tumor suppressive functions, challenging the efficacy of stromal-targeting therapies. In
addition, there is increasing appreciation for the dual role of stromal mesenchymal cells in muscle homeostasis
and regeneration, as well as in muscle wasting diseases, including cancer cachexia. Progress in tackling PDAC
will require new knowledge of its macroenvironment encompassing crosstalk between the tumor and peripheral
tissues. In Project 3, we posit the IL6/STAT3 pathway is a key pathway involved in PDAC macroenvironment
cross-talk. Synergistic interactions with the Projects and Cores in this Program Project will allow us to test the
hypothesis that STAT3 signaling in stromal mesenchymal cells present in the tumor and muscle is a component
of a feed-forward loop in the tumor macroenvironment that favors PDAC progression and cancer cachexia.

## Key facts

- **NIH application ID:** 10898573
- **Project number:** 5P01CA236778-04
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Michael C. Ostrowski
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $475,342
- **Award type:** 5
- **Project period:** 2021-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10898573

## Citation

> US National Institutes of Health, RePORTER application 10898573, Project 3 – Stromal derived IL-6/STAT3 signaling in the development and progression of PDAC (5P01CA236778-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10898573. Licensed CC0.

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