What moves wasting muscle?

Muscle wasting in cancer patients is often under-exposed compared to the direct effects of the disease and the heavy treatment program patients are in. However, muscle wasting in cancer patients has been estimated to be responsible for approximately 20% of deaths in cancer. Moreover, muscle wasting reduces the quality of life of the patients. Therefore, minimizing muscle wasting is a key element in the survival and quality of life of cancer patients.

This project aims at getting insights into the fundamental processes underlying this cancer-induced muscle wasting and consists of two integrated research lines.

Retrospective research line
The first research line focusses on the relation between body composition (amount of fat, muscle and other tissue in the patient) and side-effects due to chemotherapy. Chemotherapy is commonly used to fight tumours in an advanced state of cancer. The drugs used for the chemotherapy are either water of fat soluble. This means they may distribute differently over the fat mass or the more watery (muscle and organs) mass of the patient. Currently, the drugs are administered based on a calculation that estimates total body volume. So if a person has a low fat percentage and receives a relatively more fat- than water soluble drug, this may lead to high local concentrations of this drug. This might lead to side-effects. On the other hand, if this same patient would have a high percentage of fat mass, the local dose might be too low, leading to a decrease in effectiveness. If also the muscle mass changes and the water soluble compartment becomes smaller, this might result in severe changes in water to fat ratio in obese people. So here, muscle wasting (both in lean and overweight/obese) patients is possibly an important factor for treatment of cancer patients.
Aim of this research line is to test whether this relation between body composition (amount of fat, muscle and other tissue in the patient) and side-effects due to chemotherapy exists. We will do this by measuring body composition in CT-scans which are made for tumour diagnosis and side-effects reported in patient files.

Translational research line
Next to the retrospective research line, we have a translational research line comparing muscle function and gene expression in muscle wasting in mice and men. Muscle wasting is often caused by both a reduction in food intake and an increase in energy consumption. This makes properly balanced nutrition an important part of the treatment program of cancer patients suffering from muscle wasting. To test different nutritional interventions, often a mouse model is used where tumour cells are injected in mice to simulate cachexia. To translate the results found in mouse studies, the molecular processes that are influencing the muscle wasting need to be well defined and ideally should be the same in mice and human.
In our current research, we will assess the similarities and differences between the molecular processes in mice and men and their relation to muscle mass, muscle function and body composition. Therefore, we will make a comparison of muscle and fat biopsies of mice suffering from cancer-induced muscle wasting with those of humans with colorectal cancer suffering from muscle wasting. By comparing muscle function parameters and gene expression in the different biopsies we hope to find common mediators in both the muscle and gene expression characteristics.

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