Cancer cachexia is a severe form of anorexia and muscle wasting that ultimately kills one in five cancer patients. Cachexia is tightly associated with inflammation. The major inflammatory cytokine, tumor necrosis factor - alpha (TNFa) was initially named Cachexin, because of its role in cachexia. The awareness that wasting and nutritional deficiencies are a secondary consequence of cancer, has resulted in recent efforts to attack the symptoms of the terminal stage of cancer and prolong the quality of life for unresolvable cancer.
Cancer Requires Inflammation
Cells follow one of three programs of gene expression. They can continue with tissue-specific functions, go through cell division (proliferate) or trigger systematic disassembly (apoptosis). Proliferation requires activation of a protein, the transcription factor NF-kappaB, that controls the production of dozens of genes. Activation of NF-kappaB results in inflammation, but it is also needed for the rapid growth of cells that are constantly replenished on the surfaces of the body, such as the cells that line the gut and lungs. Blocking NF-kappaB in a cancer cell results in apoptosis.
Activation of NF-kappaB is needed for stem cells in the crypts of the small intestines, for example, to produce the layer of differentiated absorptive cells of the villi. Thus, aspirin that blocks NF-kappaB has the desired effect of reducing systemic inflammation, but taken orally it also has the undesirable side-effect of locally disrupting gut tissue. Another exciting potential application of high dose intravenous aspirin is shutting down cancer.
Abnormal Metabolism Produces Inflammation
Many different nutrient deficiencies result in the same symptoms of chronic inflammation. Several of the B vitamins, for example, are involved in production and maintenance of sulfur amino acids (methionine and cysteine) and the major cellular anti-oxidant, glutatione. B vitamin deficiencies result in many physiological problems, but they also result in oxidative stress and inflammation. Vitamin C and D deficiencies also result in inflammation.
The disruption of normal tissue metabolism by metastatic cancers also results in local inflammation that in turn further supports cancer production. As cancers spread, more and more tissue is converted to an inflammatory state and the body-wide level of chronic inflammation increases.
Cachexia Results from Chronic Inflammation
It has only recently become apparent that cancer cachexia is an extreme form of chronic inflammation. Development of cachexia is associated with an increase in the signaling molecules, cytokines (TNFa, interleukins 1 and 6), released from cells triggered by activated NF-kappaB. Cachexia, in a sense, feeds on itself, as reduced consumption and malnourishment result in inflammatory deficiencies.
Reducing Inflammation May Prevent Cachexia
A recent research article used measures of systemic inflammation, e.g. C-reactive protein, to predict the progression of cachexia in cancer patients. Increases in inflammation were accompanied by degeneration of nutrition and increased mortality. The tight association between inflammation and cachexia confirm that cancer-induced inflammation is an active component in the development of cachexia and highlights the potential for alleviating the symptoms of the terminal stage of cancer by aggressive use of anti-inflammatory treatments.
Reference:
McMillan DC. Systemic inflammation, nutritional status and survival in patients with cancer. Curr Opin Clin Nutr Metab Care. 2009 Mar 21. [Epub ahead of print]
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