Cachexia of malignancy has always interested me but the cause has eluded scientists for many years. Cachexia is a wasting away of the body which can be related to cancer or non-cancerous diseases like AIDS. It's always been clear that the etiology of this syndrome had some sort of "humoral" basis which is to say it was related to some substance in the body fluids excreted by the malignant cells. A recent article discussed this topic and the identification of a circulating protein that may be the culprit (see: Why cancer patients waste away):
Tumors implanted in adult female fruit flies cause healthy ovaries to waste away. The wasting...is caused by a protein secreted by cancer cells. A protein released by tumors is what causes cancer patients to waste away, studies of fruit flies suggest. Fat and other tissues all over the body wither in people with cancer, but the reason for the wasting, also called cachexia, was not understood. Cancer cells secrete a protein called IMPL2, researchers from Harvard Medical School and the University of California, Berkeley independently report (see: Systemic Organ Wasting Induced by Localized Expression of the Secreted Insulin/IGF Antagonist ImpL2). Both teams came to the conclusion that the protein is responsible for wasting after giving fruit flies cancer. IMPL2 prevents healthy cells from responding to insulin, a hormone that stimulates cells to import sugar and burn it for energy. When levels of IMPL2 rise, fat, muscle and other tissues can no longer consume sugar and begin to waste away. Lowering IMPL2 levels reduces the amount of wasting, both groups found.
It makes perfect sense that the cachexia mechanism of this protein is to block the cellular response to insulin which is essential for cell metabolism. This discovery obviously opens up the possibility of a new treatment pathway for cachexia of malignancy which can be used in parallel with chemotherapeutic agents. The goal of treatment will be to keep the patient in a relatively healthy metabolic state so that he or she can then benefit from the drug directed at the eradication of the tumor.
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