Are lung cancer tumors hijacking the nervous system

Salk News

July 2, 2026

Are lung cancer tumors hijacking the nervous system?

New Salk scientist finds that lung cancer tumors talk directly to the nervous system to exacerbate disease-related wasting, revealing a potential target for new therapeutics

July 2, 2026

• Highlights
• Cachexia, a syndrome marked by unwanted weight loss, sickness, and loss of appetite that accompanies and amplifies chronic illness, affects roughly half of all cancer patients and is responsible for a quarter of all cancer deaths
• Incoming Salk professor discovers that some lung cancer tumors can induce cachexia by communicating directly with the brain using a lipid signaling molecule-hijacking the nervous system and impacting behavior
• Findings suggest that tumors affect the peripheral nervous system and dietary changes could be used to treat cachexia and improve outcomes in lung cancer patients

LA JOLLA-According to the Cleveland Clinic, a quarter of cancer deaths can be attributed to one source: cachexia. Cachexia is a syndrome that accompanies underlying chronic illness and causes unwanted muscle and fat loss, reducing quality of life and sometimes even limiting treatment options. A new study led by Thales Papagiannakopoulos, PhD, an incoming Salk professor, points to a potential new target for preventing cachexia.

Stefan Kotschi (left), Thales Papagiannakoupolos (center), and Michael Cross (right) find lung cancer tumors talk directly to the nervous system to exacerbate disease-related wasting, revealing a potential target for new therapeutics.
Click here for a high-resolution image.
Credit: New York University

The researchers found that a common genetic subset of lung cancer is more prone to cachexia and that tumors from this subtype talk to the brain through sensory neurons in the lung. Silencing these sensory nerves to disrupt the tumor-to-brain connection reduced cachexia, as did blocking the production of the lipid signaling molecule prostaglandin E2 (PGE2) through dietary changes. The team suspects that the tumors use PGE2 to communicate with the nervous system, suggesting that blocking this communication could be a powerful therapeutic strategy to improve patient outcomes.

The study was published in Science on July 2, 2026.

"These lung cancer tumors are essentially controlling human behavior by tapping into the nervous system and hijacking local lung sensory neurons," says senior author Papagiannakopoulos, who conducted the research at the New York University (NYU) 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."

What did we already know about cachexia?

A 2015 German study reported that cachexia affects roughly half of cancer patients and also accompanies other chronic illnesses, like Alzheimer's disease or cardiovascular disease-ultimately impacting roughly 9 million people globally.

Cachexia begins with a high demand for energy-during chronic illness, the body suddenly needs much more energy to fuel the necessary immune response. From there, patients often experience appetite loss, and their muscles and fat begin to wane as the body eats them up to fuel its fight.

These symptoms have long been assumed to be the neurological effects of circulating immune factors associated with chronic illness. But this assumption was mostly owing to a lack of laboratory models that would provide deeper insight into the mechanisms underlying cachexia. Existing models for studying cachexia in cancer often have tumors growing in the wrong locations, and at sizes that aren't to scale with human counterparts.

"By creating a model of cachexia that is more physiologically relevant, we can make more specific, relevant discoveries," says first author Michael Cross, a graduate student researcher in Papagiannakopoulos' lab at NYU. "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."

How does a lung tumor talk to the brain?

The researchers started by developing the most physiologically relevant mouse models of lung cancer to date-ones where tumors grow in the appropriate locations, at reasonable sizes. They looked at several different subtypes of lung cancer and found that one subtype was promoting cachexia while the others were not.

New research from Thales Papagiannakopoulos finds some lung cancer tumors can hijack the nervous system, in turn impacting behavior and exacerbating disease-related wasting.
Click here for a high-resolution image.
Credit: Amy Cao

Since these mice were eating less, the researchers tried increasing the calorie and fat content of their chow to help them gain weight. To their surprise, the high-fat, high-calorie diet made things worse. Why?

Papagiannakopoulos recalled a recent finding by a collaborator showing that sensory neurons in the lungs could sense the flu, communicate that to the brain, and promote sickness and cachexia symptoms. He wondered, could this lung-brain superhighway carry messages from cancer cells, too?

To find out, the team delved straight into the nervous system. They tested whether blocking half the sensory connections between the lungs and the brain or fully deactivating the lung-based nerves would alleviate cachexia symptoms. And they did.

"Well, then we had more questions," says Papagiannakoupolos. "What is the signal that the tumors are sending to the nerves? And why is it worse with a high-fat diet?"

The cachexia-promoting lung cancer subtype was producing much higher levels of PGE2 than the other tumor subtypes. PGE2 is well known for inducing symptoms of infection, including fever. When the team modified the model mice genetically so they could no longer produce PGE2, cachexia did not develop. Cachexia also did not develop in smaller trials in which mice were given aspirin and ibuprofen, which block the body's ability to make PGE2.

Cachexia could also be prevented with dietary changes. PGE2 is derived from animal fats, like omega-6 fatty acids. By switching from high-fat diets to those that contain only omega-3 fatty acids instead, the body's ability to make PGE2 was limited, and the tumors could no longer use the signaling molecule to communicate with the nervous system and brain to cause cachexia.

Could a dietary switch change cancer outcomes?

The research unlocks an entirely new therapeutic area for treating cachexia and improving lung cancer care. Foundational studies like this can also reveal new uses for existing medications, such as aspirin and ibuprofen, and show how simple lifestyle changes can alter disease outcomes.

"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," says Stefan Kotschi, MD, a postdoctoral researcher in Papagiannakopoulos' lab at NYU.

"Once we identify those neurons and circuits," explains Papagiannakopoulos, "we could see whether they are also involved in other symptoms cancer patients experience, like depression or memory loss."

By understanding the fundamental biology of how cancer-induced cachexia signals between the lungs and brain, and how dietary changes may improve patient outcomes, scientists can identify new molecules and pathways for potential therapies. Over time, these discoveries may help researchers develop more tailored treatments that can improve cancer care in the long term.

Other authors and funding

Other authors include Warren Wu, Fedra Luciano-Mateo, Ezequiel Dantas, Taha Niazi, Shijia Chen, Ali Rashidfarrokhi, Jack Sanford, Jeshua Kim, Begona Gammallo-Lana, Adam Mar, Yuan Hao, Sahith Rajalingam, Annie Huang, Jackie Shan, Habon Issa, Kwok-Kin Wong, Leopoldo Segal, Marcus Goncalves, and Robert Froemke of NYU; Young-Yon Kwon, Juliya Hsiang, and Sheng Hui of Harvard University; Ray Pillai of NYU and VA New York Harbor Healthcare; Maria Gomez and Eileen White of Rutgers University and Princeton University; Alice Wang of Cold Spring Harbor and Stony Brook University; Xiang Zhao of Cold Spring Harbor; Tobias Janowitz of Cold Spring Harbor and Northwell Health; and Yin Liu of Howard Hughes Medical Institute.

The work was supported by the National Institutes of Health (P30CA016087, BRAIN Initiative U19NS1076, S10RR027926, S10OD032292, R37CA222504, R01CA227649, R01CA283049, R01CA262562, F30CA284910-01A1, MH019524, DA060339, 1R37CA286477, CGCSDF-2021\100003, 1OT2CA278609-01, HD088411, NS138066, NS107616, DA063565), American Cancer Society (DBG-22-173-01-TBE), Pfizer Medical Education Group (23-A0-00-1010062), German Research Foundation (KO 7112/1-1), and Princeton University.

Written by Isabella Davis Conact: [email protected]

DOI: 10.1126/science.adz4196