# Targeting the Metabolic Basis of Cachexia in Pancreatic Cancer

> **NIH NIH R01** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2020 · $454,065

## Abstract

Project Summary: Pancreatic adenocarcinomas are among the most fatal cancers because of their
extensive metastasis to distant organs, even at an early stage of tumor progression. A significant majority of
pancreatic cancer patients also suffer from a very poor quality of life due to cachexia. Cachexia not only
impedes the response to chemotherapy but also is a major cause of morbidity and mortality. Thus, a basic
understanding of the mechanisms that promote cachexia will provide a basis for developing new methods
for treatment and will significantly improve the overall quality of life.
 Tumor cells display alterations in metabolite flux into biosynthetic reactions that induce systemic
metabolic effects causing myodegeneration and adipocyte fat depletion. Although some studies have
attempted to understand the mechanistic basis of muscle and fat degradation, the metabolic link between
the energy need of tumor cells and cachexia syndrome remains largely unexplored. Our preliminary studies
identify a number of key metabolic pathways that have increased flux in tumor tissues and muscle
specimens from pancreatic cancer patients with cachexia, in comparison to the ones without cachexia.
Furthermore, our results suggest that secreted small-molecule metabolites possess cachectic activity
independent of the known cachectic agents. Hence, we hypothesize that metabolic flux in tumors and
secreted metabolites lead to metabolic alterations in muscle tissues, causing oxidative damage and
cachexia. Furthermore, we hypothesize that targeting the metabolic pathways in tumor cells and
muscles will diminish cachexia in pancreatic cancer.
 To test these hypotheses, we propose to elucidate the direct role of metabolites/metabolic pathways
in regulating cachexia (Aim 1), to test if catabolic pathways in muscles can be targeted to abrogate
cachexia in animal models (Aim 2), and to determine if elevated levels of metabolites in muscle tissues
correlate with cachexia onset and prognosis in pancreatic cancer patients (Aim 3). We will validate the
increased levels of identified tumor cell-secreted metabolites in the plasma specimens from cachectic
cancer patients in comparison to that of the non-cachectic cancer patients and characterize the mechanistic
aspects of direct myodegeneration caused by such metabolites in animal models. We will also determine if
their levels correlate with the extent of myodegeneration in patients. Furthermore, we propose to evaluate
the therapeutic efficacy of targeting the underlying metabolic pathways for diminishing cachexia. Overall,
these studies will utilize highly innovative concepts and approaches to address the role of metabolites and
metabolic pathways in cancer cachexia and evaluate the therapeutic efficacy of targeting these pathways to
diminish cancer cachexia.

## Key facts

- **NIH application ID:** 9830037
- **Project number:** 5R01CA210439-04
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** Pankaj Kumar Singh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $454,065
- **Award type:** 5
- **Project period:** 2016-12-16 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9830037

## Citation

> US National Institutes of Health, RePORTER application 9830037, Targeting the Metabolic Basis of Cachexia in Pancreatic Cancer (5R01CA210439-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9830037. Licensed CC0.

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