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Open AccessArticle

Mathematical Model of Muscle Wasting in Cancer Cachexia

Department of Mathematics, Ryerson University, 350 Victoria St, Toronto, ON M5B 2K3, Canada
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Author to whom correspondence should be addressed.
J. Clin. Med. 2020, 9(7), 2029; https://doi.org/10.3390/jcm9072029
Received: 1 May 2020 / Revised: 17 June 2020 / Accepted: 19 June 2020 / Published: 28 June 2020
Cancer cachexia is a debilitating condition characterized by an extreme loss of skeletal muscle mass, which negatively impacts patients’ quality of life, reduces their ability to sustain anti-cancer therapies, and increases the risk of mortality. Recent discoveries have identified the myostatin/activin A/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 been 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 cachectic factors. The model formulation tracks the intercellular interactions between cancer cell, satellite cell, and muscle cell populations. The model is parameterized by fitting to colon-26 mouse model data, and the analysis provides insight into tissue growth in healthy, cancerous, and post-cachexia treatment conditions. Model predictions suggest that cachexia fundamentally alters muscle tissue health, as measured by the stem cell ratio, and this is only partially recovered by anti-cachexia treatment. Our mathematical findings suggest that after blocking the myostatin/activin A pathway, partial recovery of cancer-induced muscle loss requires the activation and proliferation of the satellite cell compartment with a functional differentiation program. View Full-Text
Keywords: cancer cachexia; muscle wasting; mathematical oncology; mathematical modeling; dynamical systems cancer cachexia; muscle wasting; mathematical oncology; mathematical modeling; dynamical systems
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Farhang-Sardroodi, S.; Wilkie, K.P. Mathematical Model of Muscle Wasting in Cancer Cachexia. J. Clin. Med. 2020, 9, 2029.

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