Cancer cachexia is a devastating wasting syndrome consisting of significant fat and muscle loss observed in 50% of all cancers. 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 treatments for their respective cancer. Currently there are no effective treatments for this wasting syndrome, in part because of a lack of markers that could identify patients early in the wasting process. Therefore, clinicians often use non-approved medications for cancer cachexia with limited benefit. We therefore ...

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Cancer cachexia is a devastating wasting syndrome consisting of significant fat and muscle loss observed in 50% of all cancers. 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 treatments for their respective cancer. Currently there are no effective treatments for this wasting syndrome, in part because of a lack of markers that could identify patients early in the wasting process. 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 class of cancer and immune-secreted molecules that promote wasting by increasing the fat breakdown throughout the body. These signaling events support a communication between tumors and fat that fosters this cachexia. In parallel, we have identified a molecule in tumor cells that appears to act on the cells themselves as well as surrounding immune cells within a tumor to support this fat wasting. This molecule represents the first true tumor marker for cachexia. In 246 lung cancer patients, this marker accurately predicted which patients would and would not demonstrate cachexia/wasting at cancer diagnosis. Our proposal will elucidate how this new marker for cachexia acts in tumor cells and on immune cells surrounding these tumor cells to promote the wasting of fat in this group of patients. We will use tumors derived from lung cancer patients and animal models to study this marker and its effect on cachexia. Such knowledge may help us develop new therapeutics for this under-treated syndrome that would improve patient quality of life and survival.

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