The Biology of Cancer Cachexia and the Role of TNF-α

摘要: Cachexia, or wasting, is the most common syndrome resulting from human malignancies, estimated to contribute nearly a quarter of all cancer deaths. Although cachexia has been clinically diagnosed for more than century, it only relatively recently that investigators have begun unraveling molecular mechanisms underlying wasting state predominates in adipose and skeletal muscle tissues. Tumor necrosis factor-α, TNF-α considered leading mediator cachexia. This cytokine produced by tumor, immune, stromal cells provide growth survival advantage within tumor microenvironment. It also functions an autocrine paracrine fashion muscles regulate tissue breakdown. TNF-induced fat catabolism largely regulated through feeding response control gene expression differentiate maintain homeostasis tissue. Regulation ubiquitin-proteasome system, whose activity may be controlled TNF. Elucidation TNF signaling pathway provided further insight into regulation One effector this particular, NF-kB, appears essential TNF-mediated decay. Understanding which NF-kB reveal still other novel therapeutic targets used combination with currently existing anti-TNF therapy.