Cachexia


Clinical Background

Cachexia is the loss of weight often seen in cancer patients. The formal definition of cachexia is the loss of body mass that cannot be reversed nutritionally. Cachexia increases the probability of death and infection as well as weakening the patient and reducing quality of life. As with many of the other side effects associated with cancer and cancer therapy, cachexia is thought to be driven by the cytokines of the inflammatory cascade, tumor necrosis factor-alpha (TNF-α) – Interferon gamma (IFNγ), and Interleukin 6 (IL-6), in addition to tumor derived factors such as proteolysis inducing factor (PIF). At this time there are limited treatment options for cancer-related cachexia. Treatment often takes a multi-pronged approach, including nutritional supplementation, appetite stimulants, and a physical activity regimen. Additionally, Thalidomide, a TNF-α synthesis inhibitor, has been found to attenuate cachexia in patients with advanced pancreatic cancer.

Preclinical Models

Model Description Length Endpoints
Chemotherapy- Induced Cachexia
Treatment with either a single cycle or two cycles of doxorubicin 15 – 36 days Weight

 

Chemotherapy-Induced Cachexia

The chemotherapy drug doxorubicin is used to treat many different types of cancer, including certain types of bladder, breast, lung, stomach, and ovarian cancer; Hodgkin’s lymphoma (Hodgkin’s disease) and non-Hodgkin’s lymphoma (cancer that begins in the cells of the immune system); and certain types of leukemia. Weight loss is one of the side effects of doxorubicin treatment in humans and it also occurs in mice following administration, making doxorubicin treatment an appropriate animal model for cachexia. In this model, mice are given IP injections of doxorubicin as a single cycle (days 1-3) or for two cycles (days 1-3 and 10-12) and their weights are monitored daily for the duration of the study.

Mean Percent Body Weight Change

*Percent body weight change as a result of two cycles of doxorubicin treatment (days 1-3 and 10-12)