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 chemotherapy, but also a shorter survival time than is found in patients with comparable tumors without weight loss. Although anorexia is common, a decreased food intake alone is unable to account for the changes in body composition seen in cancer patients, and increasing nutrient intake is unable to reverse 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 wasting in cachexia. These include cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interferon-γ (IFN-γ) and leukemia inhibitory factor (LIF), as well as tumor-derived factors such as lipid mobilizing factor (LMF) and protein mobilizing factor (PMF), which can directly mobilize fatty acids and amino acids from adipose tissue and skeletal muscle respectively. Induction of lipolysis by the cytokines is thought to result from an inhibition of lipoprotein lipase (LPL), although clinical studies provide no evidence for an inhibition of LPL in the adipose tissue of cancer patients. Instead there is an increased expression of hormone sensitive lipase, the enzyme activated by LMF. Protein degradation in cachexia is associated with an increased activity of the ATP-ubiquitin-proteasome pathway. The biological activity of both the LMF and PMF was shown to be attenuated by eicosapentaenoic acid (EPA). Clinical studies show that this polyunsaturated fatty acid is able to stabilize the rate of weight loss and adipose tissue and muscle mass in cachectic patients with unresectable pancreatic cancer. Knowledge of the mechanism of cancer cachexia should lead to the development of new therapeutic agents.
About half of all cancer patients experience a wasting syndrome called cachexia in which the tumor induces metabolic changes in the host leading to loss of adipose tissue and skeletal muscle mass. Patients with pancreatic and gastric cancer have the highest frequency of weight loss (83–87%) (De Wys et al. 1980), and in patients with pancreatic cancer weight loss (14%) is evident at the time of diagnosis, and is progressive, increasing to a median of 24.5% just before death (Wigmore et al. 1997). Patients with more than 15% weight loss are likely to have significant impairment of respiratory muscle function, which is probably the major contributor to the shortened survival time of cancer patients with weight loss (De Wys et al. 1980). Gender related differences in the rate of weight loss in nonsmall cell lung cancer is responsible for the significantly shorter survival time in men than women (40 versus 78 weeks after diagnosis) (Palomeres et al. 1996). Thus a knowledge of the mechanism(s) of cancer cachexia could lead to the development of agents which would increase the survival time of cancer patients, without necessarily having an antitumor effect.