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Indeed, as cancer cells rely on external sources of nitrogen and carbon skeleton to grow, systemic metabolic deregulation promoting tissue wasting and metabolites mobilization ultimately supports tumor growth. Cachectic patients experience a wide range of symptoms affecting several organ functions such as muscle, liver, brain, immune system and heart, collectively decreasing patients\u2019 quality of life and worsening their prognosis. Moreover, cachexia is estimated to be the direct cause of at least 20% of cancer deaths. The main aspect of cachexia syndrome is the unstoppable skeletal muscle and fat storage wasting, even with an adequate caloric intake, resulting in nutrient mobilization \u2013 both directly as lipid and amino acids and indirectly as glucose derived from the exploitation of liver gluconeogenesis \u2013 that reaches the tumor through the bloodstream. From a metabolic standpoint, cachectic host develops a wide range of dysfunctions, from increased insulin and IGF-1 resistance to induction of mitochondrial uncoupling proteins and fat tissue browning resulting in an increased energy expenditure and heat generation, even at rest. For a long time, cachexia has been merely considered an epiphenomenon of end-stage tumors. However, in specific tumor types, such as pancreatic cancers, it is now clear that patients present markers of tissue wasting at a stage in which tumor is not yet clinically detectable, and that host amino acid supply is required for tumor growth. Indeed, tumor cells actively promote tissue wasting by secreting specific factors such as parathyroid hormone-related protein and micro RNAs. Understanding the molecular and metabolic mediators of cachexia will not only advance therapeutic approaches against cancer, but also improve patients\u2019 quality of life.<\/jats:p>","DOI":"10.1038\/oncsis.2016.3","type":"journal-article","created":{"date-parts":[[2016,2,22]],"date-time":"2016-02-22T09:22:43Z","timestamp":1456132963000},"page":"e200-e200","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":495,"title":["Understanding cachexia as a cancer metabolism syndrome"],"prefix":"10.1038","volume":"5","author":[{"given":"P E","family":"Porporato","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,2,22]]},"reference":[{"key":"BFoncsis20163_CR1","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.cmet.2012.06.011","volume":"16","author":"KC Fearon","year":"2012","unstructured":"Fearon KC, Glass DJ, Guttridge DC . 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