# Training and Research on Mechanisms of Pancreatic Cancer Associated Muscle Wasting and Related Therapies

> **NIH NIH K01** · UNIVERSITY OF ROCHESTER · 2021 · $142,703

## Abstract

Abstract
Skeletal muscle wasting (SMW) is a growing burden among cancer survivors and is prognostic of treatment
failure, radiotherapy toxicity, and a shorter time to tumor progression related to survival. This is of particular
concern for patients with pancreatic ductal adenocarcinoma (PDAC), for whom interventions for severe
SMW are now being implemented prior to surgery, radiation and chemotherapy, so that these patients can
complete their prescribe treatments. Currently, the mechanism(s) that lead to cancer-related SMW have
yet to be elucidated. Furthermore, viable treatment options for patients with this multifactorial syndrome
remain undiscovered. A lack of preclinical models that recapitulate human disease is often identified as an
obstacle in the development of feasible therapies to treat cancer-related SMW. To this end, our lab
developed a murine model of PDAC-related SMW that parallels human pathology and can be longitudinally
assessed via Dual Energy X-ray Absorptiometry (DEXA). In this murine model of PDAC we have identified
upregulation of pro-inflammatory cytokines, immune cell infiltration, IGFBP-3, and intramuscular
adipogenesis as key features in the progression of SMW. In addition, we determined that a single
intratumoral injection of IL-12 reduced tumor burden, pro-inflammatory signaling, and SMW, while
improving survival out to 50 days. Although a relationship between chronic low grade inflammation and
PDAC-related SMW has been suggested, the mechanisms are unknown. Also, the relationship betwe en
macrophage associated increases in IGFBP-3 and adipogenesis have yet to be investigated. Thus, the
purpose of this proposal is to investigate a novel pathway of SMW and increased intramuscular
adipogenesis via pathologic increases in IGFBP-3 by tumor and immune cells. In addition, we seek to
determine the efficacy of a multi-dose IL-12 treatment regimen to ameliorate SMW through the reduction
of inflammation, intramuscular macrophage infiltration, IGFBP-3 secretion, and adipogenesis in a murine
model of PDAC.

## Key facts

- **NIH application ID:** 10299703
- **Project number:** 1K01CA240533-01A1
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Calvin Lloyd Cole
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $142,703
- **Award type:** 1
- **Project period:** 2021-08-09 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10299703

## Citation

> US National Institutes of Health, RePORTER application 10299703, Training and Research on Mechanisms of Pancreatic Cancer Associated Muscle Wasting and Related Therapies (1K01CA240533-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10299703. Licensed CC0.

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