Cancer cachexia is a devastating wasting syndrome consisting of significant fat and muscle loss affecting 50% of all cancer patients. It is responsible for 1/3 of all cancer related deaths. Cancer patients with cachexia live half as long as patients with the same cancers without cachexia. These emaciated patients have a poor quality of life which precludes them from receiving standard of care treatments for their respective cancer. Currently there are no effective treatments for this wasting syndrome. Therefore, clinicians often use non-approved medications for cancer cachexia with limited benefit. We therefore sought to better understand how cancers can cause cachexia wasting in orde...

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Cancer cachexia is a devastating wasting syndrome consisting of significant fat and muscle loss affecting 50% of all cancer patients. It is responsible for 1/3 of all cancer related deaths. Cancer patients with cachexia live half as long as patients with the same cancers without cachexia. These emaciated patients have a poor quality of life which precludes them from receiving standard of care treatments for their respective cancer. Currently there are no effective treatments for this wasting syndrome. Therefore, clinicians often use non-approved medications for cancer cachexia with limited benefit. We therefore sought to better understand how cancers can cause cachexia wasting in order to provide a rationale for more effective medications. Our studies have identified a cancer-secreted molecule that promotes wasting by increasing the breakdown of triglycerides in fat tissue and by altering food intake. This cancer-secreted factor imitates the wasting by acting directly on the fat and the part of the brain that controls appetite. This factor also reprograms the fat to secrete other factors that also affect the brain’s appetite center. We believe the combination of these events is responsible for the wasting seen in these cancer patients. Our proposal will elucidate the biologic pathways occurring in the fat tissue and the brain that drive cancer cachexia. Identifying common pathways used to activate these tissues by the cancer will help us develop new therapeutics for this under-treated disease. Establishing an effective treatment for cancer cachexia will improve patients’ quality of life and overall survival.

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