Vagus nerve modulation can effectively halt the progression of cancer-associated cachexia

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. 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. Ali Khademhosseini, Director and CEO, Terasaki Institute for Biomedical Innovation

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.