A new study led by Thales Papagiannakopoulos, PhD, an incoming Salk professor, identifies a potential target for preventing cachexia in lung cancer patients, according to findings published in Science on July 2. The research highlights that a common genetic subset of lung cancer is more susceptible to cachexia and that these tumors communicate with the brain through sensory neurons in the lung.
The team found that silencing these sensory nerves or blocking the production of prostaglandin E2 (PGE2), a lipid signaling molecule, reduced symptoms of cachexia. Dietary changes limiting PGE2 production also lessened cachexia effects. "These lung cancer tumors are essentially controlling human behavior by tapping into the nervous system and hijacking local lung sensory neurons," said Papagiannakopoulos, who conducted the research at New York University Grossman School of Medicine. "This role of the peripheral nervous system in cancer cachexia is entirely novel, and I think it could point us to really exciting translational opportunities that could drastically improve cancer care."
Cachexia is a syndrome characterized by unwanted muscle and fat loss during chronic illness, which can reduce quality of life and limit treatment options. According to the Cleveland Clinic, about one quarter of all cancer deaths are attributed to this condition.
Michael Cross, first author and graduate student researcher in Papagiannakopoulos' lab at NYU, said: "By creating a model of cachexia that is more physiologically relevant, we can make more specific, relevant discoveries. Like finding that one subtype of lung cancer tumors promotes cachexia more than others, and that those tumors actually locally communicate with the peripheral nervous system." A 2015 German study reported that roughly half of all cancer patients experience cachexia.
The researchers used mouse models with physiologically relevant tumor locations and sizes to examine different subtypes of lung cancers. They observed increased levels of PGE2 in certain tumor subtypes linked with greater risk for developing cachexia. Genetic modifications eliminating PGE2 production prevented development of symptoms; similarly, administering aspirin or ibuprofen—both known inhibitors—also blocked onset.
Stefan Kotschi, MD, postdoctoral researcher at NYU involved in the study, said: "Now that we know tumors are hijacking the nervous system, we want to pinpoint exactly which neurons they use to do that and what circuits in the brain they connect to." Papagiannakopoulos added: "Once we identify those neurons and circuits...we could see whether they are also involved in other symptoms cancer patients experience like depression or memory loss." The researchers suggest understanding this communication pathway may help develop new therapies for improving outcomes among people affected by both lung cancers and related syndromes.
