Cancer cachexia

Abstract

Cancer cachexia is a complex syndrome that includes host tissue wasting, anorexia, asthenia, and abnormal host intermediary metabolism. It is present in approximately 50% of cancer patients during treatment and nearly 100% of treated cancer patients at death. Cachexia has a detrimental impact on cancer therapy. The central problem of cancer cachexia is that energy balance is not maintained, and the host has a relative hypophagia which results in host tissue wasting. The tumor by its nature and obligate growth can continue to consume glucose, amino acids, and lipids at the expense of the host. This produces abnormal host intermediary metabolism including elevated glucose production and recycling, decreased muscle protein synthesis, and increased muscle and fat breakdown. The exact mechanisms of cancer cachexia have been only partially elucidated. The identification of signal molecules like cachectin which mediate these changes may be on the horizon. Nutritional support can reverse some of the derangements seen with cachexia, and there is evidence that functional lean body mass or body cell mass can be restored in some (but not all) patients. However, nutritional support has not yet improved response to chemotherapy or radiation therapy, nor has it improved host tolerance of chemotherapy. It has improved operative mortality and morbidity in cachectic cancer patients undergoing major surgical procedures. Optimum host nutritional support appears to be dependent on high insulin concentrations in both humans and rats. Insulin and exercise may be methods to preserve host lean tissue and feed the host rather than the tumor. Future studies depend on better definition of tumor-bearing host metabolism, altering the relationship between neoplasm and host to preferentially feed the host, and making the neoplasm more susceptible to effective treatment.

Evidence for the involvement of interleukin 6 in experimental cancer cachexia.

“…Cancer cachexia, which includes depletion of muscle and fat tissue, anorexia, asthenia, hypoglycemia and anemia (1,2), complicates therapeutic intervention (3) and is an important cause of death in cancer patients (4). Host-derived and tumor cell-derived tumor necrosis factor (TNF)' has been suggested as a mediator of the metabolic changes associated with cachexia because it can suppress key metabolic enzymes and can induce cachexia in experimental animals (5-7).…”

Evidence that tumor necrosis factor plays a pathogenetic role in the paraneoplastic syndromes of cachexia, hypercalcemia, and leukocytosis in a human tumor in nude mice.

“…Two ofthe most common are cachexia (3) and hypercalcemia (4). In addition to cachexia and hypercalcemia, leukocytosis is also a relatively common paraneoplastic syndrome (5).…”

Metabolic effects of cachectin/tumor necrosis factor are modified by site of production. Cachectin/tumor necrosis factor-secreting tumor in skeletal muscle induces chronic cachexia, while implantation in brain induces predominantly acute anorexia.

“…The syndrome of "cachexia" is characterized by weight loss, anorexia, anemia, and net losses ofbody protein and lipid; its prevalence exceeds 70% for certain types of cancer, and is even higher in patients suffering with AIDS (1)(2)(3)(4)(5). Cachectic patients may lose > 50% of their preillness body weight, and the onset of malnutrition and inanition accelerates their demise.…”