Wasting in cancer

Progressive weight loss is a common feature of many types of cancer and is responsible not only for a poor quality of life and poor response to chemot herapy, but also a shorter survival time than is found in patients with com parable tumors without weight loss. Although anorexia is common, a decrease d food intake alone is unable to account for the changes in body compositio n seen in cancer patients, and increasing nutrient intake is unable to reve rse the wasting syndrome. Although energy expenditure is increased in some patients, cachexia can occur even with a normal energy expenditure. Various factors have been investigated as mediators of tissue cytokines such as tu mor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interferon-gam ma (IFN-gamma) and leukemia inhibitory factor (LIF), as well as tumor-deriv ed factors such as lipid mobilizing factor (LMF) and protein mobilizing fac tor (PMF), which can directly mobilize fatty acids and amino acids from adi pose tissue and skeletal muscle respectively. Induction of lipolysis by the cytokines is thought to result from an inhibition of lipoprotein lipase (L PL), although clinical studies provide no evidence for an inhibition of LPL in the adipose tissue of cancer patients. Instead there is an increased ex pression of hormone sensitive lipase, the enzyme activated by LMF, Protein degradation in cachexia is associated with an increased activity of the ATP -ubiquitinproteasome pathway, The biological activity of both the LMF and P MF was shown to be attenuated by eicosapentaenoic acid (EPA), Clinical stud ies show that this polyunsaturated fatty acid is able to stabilize the rate of weight loss and adipose tissue and muscle mass in cachectic patients wi th unresectable pancreatic cancer. Knowledge of the mechanism of cancer cac hexia should lead to the development of new therapeutic agents.