Cutting-edge research from Salk Institute in La Jolla, California, has identified a potential new target for preventing cachexia — a condition marked by severe sickness, loss of appetite and unwanted muscle, fat and weight loss that accompanies and amplifies all sorts of chronic illness. According to Cleveland Clinic, approximately half of all cancer patients experience cachexia, and one quarter of all cancer patients die from its complications.
Now, a study published in Science reveals patients with a common genetic type of lung cancer are more prone to developing cachexia. The paper, “A Dietary Switch Promotes Sensory Neuron–Dependent Cancer-Associated Cachexia,” details how these cancerous lung tumors take over the nervous system, communicating with the brain through sensory neurons in the lungs.
In a Salk news release, lead investigator and senior author Thales Y. Papagiannakopoulos, PhD, said this discovery opens doors to a novel therapy that can target the lungs’ sensory neurons to reduce the risk of cachexia.
“These lung cancer tumors are essentially controlling human behavior by tapping into the nervous system and hijacking local lung sensory neurons,” said Dr. Papagiannakopoulos, who is an associate professor in the department of pathology at NYU Grossman School of Medicine and a member of Perlmutter Cancer Center. “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.”
Dr. Papagiannakopoulos and his team began by developing mouse models of lung cancer that had lung tumors in the most accurate sizes and locations. This allowed them to examine different lung cancer subtypes with precision and observe that one subtype, in particular, increasingly promoted cachexia.
“By creating a model of cachexia that is more physiologically relevant, we can make more specific, relevant discoveries,” said Michael Cross, a graduate research student in Papagiannakopoulos’ lab at NYU.
Thales Y. Papagiannakopoulos, PhDNew York University
When they genetically or surgically altered the mouse models to suppress the vagus nerve and stop PGE2 production, the researchers found that cachexia did not develop. In another experiment, the researchers gave mice aspirin and ibuprofen, which blocked the body’s ability to make PGE2, and cachexia also failed to occur.
They also found they could reduce the risk of cachexia by imposing a diet limited in animal fats, such as omega-6 fatty acids, which also produce PGE2. Diets rich in omega-3 fatty acids reduced PGE2 levels and the presence of cachexia.
“Even though blocking prostaglandin E2 did not shrink the tumors, it made the mice stronger and more able to tolerate the toll lung cancer was taking on their bodies,” Dr. Papagiannakopoulos said in a NYU news release.
To further its findings, Papagiannakopoulos’ lab team examined lung fluid samples from human lung cancer patients with cachexia, which also showed heightened PGE2 levels. This suggests interference of PGE2 signaling or production would likely be beneficial in humans as well.
“We hope our research illuminates ways to treat cachexia by blocking harmful signals to the vagus nerve and dietary interventions, so we can help patients be as strong as possibly as they fight cancer,” he said.
Dr. Papagiannakopoulos said the study helped understand the mechanical biology of how lung cancer tumors can trigger cachexia. Thereby, obstructing the tumor-to-brain line of communication could prove to be a critical strategy that improves patient quality of life and outcomes, he said.
