Cancer anorexia and cachexia.
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.
Tisdale
M J
MJ
Pharmaceutical Sciences Research Institute, Aston University, Birmingham, United Kingdom.
D000855:Anorexia / Q000209:etiology* / Q000378:metabolism / Q000628:therapy; D019167:Appetite Stimulants / Q000627:therapeutic use; D001798:Blood Proteins / Q000378:metabolism; D002100:Cachexia / Q000209:etiology* / Q000378:metabolism / Q000628:therapy; D004537:Eicosanoic Acids / Q000627:therapeutic use; D006801:Humans; D050356:Lipid Metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D010455:Peptides / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D011509:Proteoglycans
D019167:Appetite Stimulants; D001798:Blood Proteins; D004537:Eicosanoic Acids; D010455:Peptides; D011506:Proteins; D011509:Proteoglycans; C008287:lipid mobilizing substance; C042057:proteolysis-inducing peptide