Lung tumors hijack the nervous system to induce fatal wasting

Cachexia, the severe loss of muscle and fat often seen in cancer patients, frequently leaves individuals too frail to tolerate life-saving treatments. While the condition is a leading cause of death in oncology, its biological drivers have remained elusive. The research team identified that LKB1-deficient lung tumors produce high levels of prostaglandin E2, a signaling molecule that amplifies inflammation.

Unlike systemic effects that circulate through the blood, this process relies on short-range communication. Prostaglandin E2 acts locally in the lungs, stimulating neurons connected to the vagus nerve, which then relays distress signals to the brain. By blocking these signals—using NSAIDs, omega-3 fatty acids, or surgical suppression of the vagus nerve—the team successfully mitigated weight loss and improved survival rates in mouse models, even when the tumors themselves were not reduced in size. Testing of lung fluid from human patients confirmed higher levels of prostaglandin E2 in those experiencing cachexia, suggesting that targeting this pathway could eventually offer a new clinical approach to help patients maintain the strength necessary to fight cancer.