Overview of cancer cachexia

Fabbro, Egidio Del; Inui, Akio; Strasser, Florian

doi:10.1007/978-1-910315-07-1_1

Cited by 2 publications

(1 citation statement)

References 16 publications

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“…Generally, an unintended body weight loss of more than 5% in a year is considered cachexia [1,5]. The dramatic weight loss causes increased disease symptoms such as pain, weakness, and fatigue [16] and leads to limited treatment options [17,18].…”

Section: Introductionmentioning

confidence: 99%

Mathematical Model of Muscle Wasting in Cancer Cachexia

Farhang‐Sardroodi

Wilkie

2020

JCM

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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.

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Section: Introductionmentioning

confidence: 99%

Mathematical Model of Muscle Wasting in Cancer Cachexia

Farhang‐Sardroodi

Wilkie

2020

JCM

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Mathematical Model of Muscle Wasting in Cancer Cachexia

Farhang‐Sardroodi

Wilkie

2020

Preprint

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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 partially recovered by anti-cachexia treatment. Our mathematical findings suggest that the activation and proliferation of satellite cells, after blocking the myostatin/activin B pathway, is required to partially recover cancer-induced muscle loss.Cancer Cachexia | Muscle Wasting | Mathematical Oncology | Mathematical Modeling |

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Overview of cancer cachexia

Cited by 2 publications

References 16 publications

Mathematical Model of Muscle Wasting in Cancer Cachexia

Mathematical Model of Muscle Wasting in Cancer Cachexia

Mathematical Model of Muscle Wasting in Cancer Cachexia

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