Illness behaviors, metabolic disturbances, and cognitive injury are common in cancer patients and frequently lead to wasting or cachexia. This devastating state of malnutrition is brought about by a synergistic combination of decreased appetite and increase in metabolism of fat and lean body mass. The severity of cachexia is often the primary determining factor in both quality of life and ultimate survival. There are currently no effective treatments for cachexia, and its mechanisms are poorly understood. Our lab has previously elucidated the actions of inflammatory cytokines, including IL-1β and TNF-α, on hypothalamic neurons and their roles in driving cachexia symptoms. However, chronic administration of these cytokines results in desensitization and loss of cachexia symptoms, demonstrating canonical inflammatory cytokines alone are insufficient for sustaining cachexia. These observations and more demonstrate that the molecular pathways responsible for driving chronic central nervous system (CNS) derangement and cachexia symptoms remain unknown.