# Skeletal Muscle Atrophy and Dysfunction in Human Cancer

> **NIH NIH R01** · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · 2021 · $462,369

## Abstract

Project Summary
Cancer and its treatment can have profound effects on skeletal muscle, the most well-recognized being
atrophy, weakness and diminished oxidative capacity. These adaptations and their functional sequelae
negatively impact quality of life, treatment decisions and survival. Despite these negative consequences, the
factors promoting these skeletal muscle adaptations remain poorly defined and understudied in human
patients. To address this gap in knowledge, our goals in this application are to: 1) to examine the role of
muscle disuse as a regulator of muscle size and function in human cancer patients and 2) to understand how
human tumor-derived factors and cancer therapeutics affect muscle biology and interact with muscle
use/mechanical stimuli to regulate skeletal muscle size and function. Based on our preliminary data, we put
forth the hypothetical model that muscle disuse accompanying cancer and its treatment plays an integral role
to facilitate muscle atrophy and dysfunction in response to tumor-derived factors and chemotherapeutics in
human patients and/or to mediate these adaptations directly. Accordingly, maintaining or increasing muscle
use will mitigate these adaptations. Three specific aims are proposed to test this model: 1) to examine the
effects of muscle disuse on skeletal muscle size, contractile function and oxidative capacity in cancer
patients receiving treatment and the effects of maintaining or increasing muscle use with exercise; 2) to
define the effects of human tumor-derived factors, cancer therapeutics on muscle cell size and mitochondrial
function and their interaction with mechanical signaling; and 3) to determine if cancer and its treatment
induce muscle contractile dysfunction through myofilament protein oxidation and whether maintaining or
increasing muscle use with exercise prevents these adaptations. To accomplish these aims, we will study
patients with non-small cell lung carcinoma longitudinally. Tissue acquired from skeletal muscle and tumor
biopsies will be used in both in vivo and in vitro experimental approaches, along with exercise/mechanical
stretch interventions. A comprehensive approach employing primary outcomes of muscle structure, function,
metabolism and signaling, ranging from molecular to whole tissue measurements, will provide data to
address these aims. Achieving our goals will advance knowledge of the cellular and sub-cellular skeletal
muscle adaptations in human cancer patients undergoing treatment and the mediators of these adaptations.
If successful, our results could shift conventional thinking in this field to include disuse as an important
effector of muscle adaptations in human cancer. Such findings could influence supportive care paradigms,
which currently focus on rehabilitating cancer patients after therapy, to support institution of activity/exercise
interventions earlier in the clinical treatment continuum to more effectively mitigate muscle adaptations and,
in turn, improve...

## Key facts

- **NIH application ID:** 10149247
- **Project number:** 5R01AR065826-05
- **Recipient organization:** UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
- **Principal Investigator:** MICHAEL J TOTH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $462,369
- **Award type:** 5
- **Project period:** 2016-07-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10149247

## Citation

> US National Institutes of Health, RePORTER application 10149247, Skeletal Muscle Atrophy and Dysfunction in Human Cancer (5R01AR065826-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10149247. Licensed CC0.

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