Cachexia and Cancer

Cachexia – the massive depletion of muscle mass and adipose tissue – is commonly seen in people with cancer and other major illnesses. Also called cancer cachexia or cancer anorexia cachexia, it is a key factor that influences the mortality and quality of life of cancer patients. It involves progressive weight loss, anorexia, and erosion of body mass triggered by a malignant growth.

People with some cancers such as gastric and pancreatic cancers are more prone to severe cachexia. These patients can lose up to 20% of their body weight. Men with cancer tend to have more profound cachexia than women with cancer.

Cancer cachexia is a metabolic defect that has gained a lot of attention in recent times, though it has always been known to exist in cancer patients. Recent advances in cachexia research have identified the catabolic factors that destroy the tissues of affected people. Cachexia is often linked to poor response to chemotherapy, reduced functional performance, and high mortality. The extent of cachexia does not seem to depend on the size of the tumor or the degree of metastasis in cancer patients.

Cancer Cachexia and Anorexia

Weight loss in cancer cachexia is different from the weight loss that results from starvation as in anorexia. Weight loss in starvation is a direct result of inadequate calorie intake. During the initial stages of starvation, the brain and erythrocytes derive energy from the glycogen in liver and muscle. In long-term starvation, the body starts using fat as a fuel, by converting fatty acids from adipose tissue to ketone bodies, thus conserving muscle mass. That is, the major weight loss in starvation is from burning fat and only a minor portion of the energy is derived from muscle.

In contrast, weight loss in cancer cachexia involves loss of equal amounts of fat and muscle. Even though anorexia is often present in cancer patients, reduced food intake is not the only factor that causes muscle wasting. This is evident from the fact that the catabolic process or muscle wasting could not be reversed with the help of nutritional supplementation or appetite manipulation. Recent studies however, did show that nutritional supplementation combined with drugs that arrest the effect of tumor factors might be helpful in reversing the tissue loss caused by cachexia.

Nutritional Support in Cancer Cachexia

Cachexia is most often linked to pre-terminal disease though it may be present during the early stages of cancer. Cancer-associated weight loss is mainly thought to be due to reduced food intake and abnormalities in the metabolism of carbohydrate, fat, and protein in the affected individuals. This metabolic defect can lead to constant depletion and ineffective repletion of adipose tissue, in spite of nutritional support.

While nutritional support is helpful in maintaining body weight, it is ineffective in maintaining the lean body mass of cancer patients. Studies do show that nutritional support enhances morbidity and mortality in people with cancer, though it does not improve response to radiation or chemotherapy.

Since cancer cachexia involves metabolic abnormalities, an effective nutritional therapy will need to manipulate the intermediary metabolism in affected individuals instead of focusing only on feeding.

Triggers of Cancer Cachexia

Cancer cachexia is believed to be mediated by inflammatory cytokines, especially tumor necrosis factor-α and IL-6 produced by tumor cells. Studies focusing on the weight loss mechanism in rabbits showed that TNF-α administration in lab rabbits induces cachexia, with anorexia and adipose tissue depletion. TNF-α has also been shown to trigger muscle protein degradation, though there was no proof of direct action.

Various animal studies have proved that interleukin 6 (IL-6) has also a potential role in cachexia development in relation to other factors.  In one particular study on mice, infusion of IL-6 did not cause weight loss in mice bearing a tumor clone that does not induce weight loss. This surprising finding thus seems to indicate that IL-6 alone was not responsible for cachexia induction.

References

• http://www.nature.com/nrc/journal/v2/n11/full/nrc927.html
• http://www.cancercachexia.com/what-is-cancer-cachexia
• http://www.ncbi.nlm.nih.gov/pubmed/3292798
• https://www.merckmanuals.com/professional/hematology-and-oncology/principles-of-cancer-therapy/cachexia-in-cancer