# The role of the macroenvironment in pancreatic cancer-induced cachexia

> **NIH NIH P01** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2024 · $1,967,038

## Abstract

PROJECT SUMMARY: OVERALL
The overall goal of this Program Project is to gain a better understanding of the underlying mechanisms that
drive cachexia in cancer patients, especially patients with pancreatic ductal adenocarcinoma (PDAC) that
exhibit one of the highest incidences of cachexia among all tumor types. Cancer patients who have lost > 5%
of their pre-illness weight are considered cachectic. In comparison, 85% of PDAC patients lose an average of
14% body weight, and recent published data show that any loss of body weight > 10% in this population leads
to poorer survival. Although some improvements have been made in PDAC to extend the 5-year survival rate,
this is still among the lowest rate of all solid tumors. Thus, until therapeutics are found to effectively treat
PDAC, understanding the causes of cachexia is vital to improving treatment responses, quality of life, and
potentially overall survival. The main innovative concept in our Program Project is the belief that to effective
treat PDAC-induced cachexia one must consider the macroenvironment of this syndrome, so as to treat the
tumor and the wasting of peripheral tissues at the same time. The effectors we focus on in this Program
Project are part of the NF-B/IL-6/STAT3 signaling axis. Our hypothesize is that the NF-B/IL-6/STAT3
signaling axis is a central regulator of the macroenvironment in PDAC-induced cachexia. This hypothesis will
be tested in 3 Projects under the support of 4 Cores. Project 1 focuses on the IL-6/STAT3 portion of the NF-
B/IL-6/STAT3 signaling axis. Specifically, studies will define the participation of IL-6 and the IL-6 receptor
acting through STAT3 to mediate fat and muscle loss. Project 2 focuses on NF-B within the signaling axis,
exploring two fresh concepts in how NF-B functions in muscle stem cells to promote local muscle
inflammation and in PDAC progression by modulating the surveillance of innate and adaptive immune cells.
Project 3 will explore the IL-6/STAT3 axis within stroma fibroblasts. Specifically, how STAT3 signaling in
stromal mesenchymal cells in the tumor and peripheral tissues produces an immunosuppressive
macroenvironment that favors PDAC progression and cancer cachexia. Core A (Administration) will provide
administrative structure for the organization of the program. Core B (Human Biospecimens) will maintain a
repository of tissues from PDAC patients with and without cachexia and support next generation sequencing
analysis. Core C (Immunophenotyping) will provide expertise in scRNA-Seq and multispectral imaging of the
tumor, skeletal muscle, and fat in PDAC-induced cachexia. Core D (Biostatistics) will provide biostatistical
support. This Program contains multiple points of integration founded on collaborations between NCI
designated Cancers Centers at the Medical University of South Carolina and Indiana University and their
respective Cancer Cachexia Programs. The outcome obtained from these studies will advance our basic
understanding ...

## Key facts

- **NIH application ID:** 10898562
- **Project number:** 5P01CA236778-04
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Denis C Guttridge
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,967,038
- **Award type:** 5
- **Project period:** 2021-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10898562

## Citation

> US National Institutes of Health, RePORTER application 10898562, The role of the macroenvironment in pancreatic cancer-induced cachexia (5P01CA236778-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10898562. Licensed CC0.

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