Mathematical model of muscle wasting in cancer cachexia incorporated with immunology
Cancer cachexia is a debilitating condition characterized by an extreme loss of skeletal muscle mass. It negatively impacts patients’ quality of life, reduces their ability to sustain anti-cancer therapies, and increases mortality risk. 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 of tumour-bearing animals.
In this mini-symposium, I will present a novel mathematical model of muscle tissue subjected to tumour-derived cachectic factors to explore the implications of this signalling pathway and potential therapeutic targets in cachexia. The model tracks the intercellular interactions between cancer, satellite, and muscle cell populations and is parameterized by fitting to colon-26 mouse model data. Our 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. Cancer cachexia is often associated with chronic inflammation, and immune cells such as macrophages and T cells have been implicated in the development and progression of this condition. Our future interest is to incorporate immune response in our cancer cachexia model, which may lead to the development of new treatments and interventions for this debilitating condition.