Cachexia is a complex metabolic condition characterised by muscle wasting and fat loss. Cancer cachexia is a major complication of cancer affecting up to 80% of patients in certain types of cancer and accounting for up to 25% of cancer deaths. We have shown that the TNF receptor family member Fn14, which is normally involved in wound healing, is a cause of cancer cachexia and inhibitory antibodies completely ablate the symptoms of cancer cachexia. We have shown that Fn14 located in the tumour is responsible for the muscle wasting and fat loss, suggesting that the activity of Fn14 in tumour cells causes the release of soluble factors into the blood stream that cause the symptoms seen in peripheral tissues. We have also shown that the Fn14 activity in tumours is independent of its normal ligand TWEAK. These observations has led us to a search of soluble factors released from tumour cells and the mechanism for auto-activation of Fn14 in tumour cells.