Lung tumors appear to drive the severe muscle and fat wasting known as cachexia by tapping directly into the nervous system, according to a study led by Thales Papagiannakopoulos, PhD, an incoming Salk professor who carried out the work at NYU Grossman School of Medicine. His team found that one common genetic subtype of lung cancer is especially prone to cachexia, and that these tumors communicate with the brain through sensory neurons in the lung itself.
When the researchers silenced those sensory nerves, breaking the tumor-to-brain line of communication, cachexia was reduced. They saw a similar effect when they used dietary changes to block production of prostaglandin E2, or PGE2, a lipid signaling molecule the team suspects tumors use as their messenger to the nervous system. That points to two possible intervention points for a syndrome that currently has no effective treatment.
The stakes are considerable. The Cleveland Clinic attributes a quarter of cancer deaths to cachexia, which erodes quality of life and can make patients too frail to tolerate treatment. A 2015 German study estimated that about half of cancer patients experience it, and that cachexia also accompanies other chronic conditions including Alzheimer's disease and cardiovascular disease, affecting roughly 9 million people worldwide.
Papagiannakopoulos describes the tumors as "essentially controlling human behavior by tapping into the nervous system and hijacking local lung sensory neurons," and calls this role for the peripheral nervous system in cachexia entirely new. Whether interrupting that signal can be translated into a therapy for patients remains the next question, but identifying a specific molecular conversation between tumor and brain gives researchers something concrete to aim at.