image: Aliesha Garrett, lead author of the study on targeting the vagal brain-liver axis to combat cancer-associated cachexia.
Credit: Terasaki Institute
Los Angeles, CA – August 14, 2025 – The Terasaki Institute for Biomedical Innovation announces a significant advancement in addressing the fight against cancer-associated cachexia (CAC), a life-threatening syndrome responsible for over one-third of cancer-related deaths. Published in Cell, the study led by Dr. Aliesha O’Raw, Principal Investigator at the Institute, demonstrates that modulating the vagus nerve can effectively halt the progression of cachexia, enhance chemotherapy outcomes, and improve survival in preclinical models.
The study, titled “Vagal Blockade of the Brain-Liver Axis Deters Cancer-Associated Cachexia,” uncovers how cancer-induced systemic inflammation disrupts vagal tone, impairing communication along the brain-liver axis. This dysregulation leads to the depletion of HNF4α, a crucial transcription factor governing liver protein metabolism. The resulting hepatic dysfunction amplifies systemic inflammation, driving the cachectic symptoms that afflict many cancer patients.
By targeting the right cervical vagus nerve through surgical, chemical, electrical, or non-invasive transcutaneous stimulation methods, the research team successfully restored vagal function. This intervention reestablished normal liver metabolism, reduced systemic inflammation, and alleviated cachexia's clinical manifestations. Importantly, combining vagus nerve modulation with chemotherapy yielded synergistic effects, significantly improving health and survival outcomes in mouse models.
“This research addresses a critical unmet need in oncology,” said Dr. Ali Khademhosseini, Director and CEO of the Terasaki Institute for Biomedical Innovation. “Cachexia has long been a devastating complication for cancer patients. Dr. O’Raw’s work not only uncovers the biological mechanisms at play but also presents a tangible intervention strategy with real potential to transform patient care.”
Dr. Aliesha O’Raw, Principal Investigator of the study, added, “This research demonstrates how neuromodulation can reshape systemic metabolism and control inflammation. Targeting the vagus nerve is a promising therapeutic approach that could be translated into non-invasive treatments to alleviate cachexia and enhance cancer therapy outcomes.”
The study reveals the essential role of the brain-liver axis in cancer-associated cachexia and presents vagus nerve modulation as a practical, patient-accessible therapeutic strategy. This innovation paves the way for future clinical trials and could redefine cachexia management in oncology.
A link to the publication can be found here
For more information, please contact:
Dr. Aliesha O’Raw
Principal Investigator
Terasaki Institute for Biomedical Innovation
Email: aoraw@terasaki.org
About the Terasaki Institute for Biomedical Innovation
The Terasaki Institute for Biomedical Innovation is a non-profit research organization that invents and fosters practical solutions that restore or enhance the health of individuals. The Institute aims to enhance the quality of human life through translational research and the acceleration of biomedical innovation. TIBI's research focuses on the development of biomaterials, cellular and tissue engineering, medical devices, and microfluidic systems.
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Journal
Cell
Method of Research
Experimental study
Subject of Research
Animals
Article Title
Vagal Blockade of the Brain-Liver Axis Deters Cancer-Associated Cachexia
Article Publication Date
7-Aug-2025
COI Statement
Duke University and Weizmann Institute of Science applied for a patent on the use of this strategy to treat CAC. Aliesha Garrett and Xiling Shen are co-founders of OnVagus, Inc., a company that is pursuing this strategy to treat CAC.