Patients with
cancer cachexia experience a profound wasting of adipose tissue and lean body mass.
Anorexia, although often present, is insufficient to account for tissue wasting because 1)
cachexia involves massive depletion of skeletal muscle that does not occur during
anorexia, 2) nutritional supplementation cannot replenish the loss of lean body mass, 3)
cachexia can occur without
anorexia, and 4) food intake might be normal for the lower weight of the
cancer patient.
Anorexia can arise from 1) decreased taste and smell of food, 2) early satiety, 3) dysfunctional hypothalamic membrane
adenylate cyclase, 4) increased brain
tryptophan, and 5)
cytokine production.
Appetite stimulants such as
cyproheptadine,
medroxyprogesterone acetate, and
megestrol acetate do not significantly improve lean body mass.
Tumor products might be more important in the development of
cachexia. Cachectic patients excrete in their urine a
lipid-mobilizing factor that directly stimulates lipolysis in a
cyclic AMP-dependent manner and increases energy expenditure. Loss of skeletal muscle in
cachexia is caused by upregulation of the
ubiquitin-
proteasome catabolic pathway.
Cachexia-inducing
tumors elaborate a sulfated
glycoprotein, which directly initiates
protein catabolism in skeletal muscle. The action of this proteolysis-inducing factor is attenuated by the
polyunsaturated fatty acid eicosapentaenoic acid, which is also effective in preventing loss of skeletal muscle in
cancer patients. Antagonists of
tumor catabolic factors will provide important new agents in the treatment of
cancer cachexia.