Mar 31, 2020

Mathematical Model of Muscle Wasting in Cancer Cachexia

BioRxiv : the Preprint Server for Biology
S. Farhang-Sardroodi, Kathleen P Wilkie

Abstract

Cancer cachexia is a debilitating condition characterized by an extreme loss of skeletal muscle mass which negatively impacts patient's quality of life, reduces their ability to sustain anticancer therapies, and increases the risk of mortality. Recent discoveries have identified the myostatin/activin-ActRIIB pathway as critical to muscle wasting by inducing satellite cell quiescence and increasing muscle-specific ubiquitin ligases responsible for atrophy. Remarkably, pharmacological blockade of the ActRIIB pathway has shown to reverse muscle wasting and prolong the survival time of tumor-bearing animals. To explore the implications of this signaling pathway and potential therapeutic targets in cachexia, we construct a novel mathematical model of muscle tissue subjected to tumor-derived cachexic factors. The model formulation tracks the intercellular interactions between cancer, satellite cell, and muscle cell populations. The model is parameterized by fitting to colon-26 mouse model data, and analysis provides insight into tissue growth in healthy, cancerous, and post-treatment conditions. Model predictions suggest that cachexia fundamentally alters muscle tissue health, as measured by the stem cell ratio, and this is only part...Continue Reading

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Mentioned in this Paper

Fluctuation
Environment
Sample Fixation
De Novo Mutation
Experience
Specialty Physician
Fixation - Action
Mutation Abnormality
Evolution, Molecular
EAF2 gene

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