Cutting both branches of the vagus nerve to the stomach or blocking its chemical signal with botulinum toxin (Botox) injections prevents the development and progression of gastric cancer in mouse models, new research shows.
The advantage of botulinum toxin is that "it can be used locally and it targets cancer stem cells," said investigator Duan Chen from the Norwegian University of Science and Technology. It can also be injected through gastroscopy, and it only requires the patient to stay in the hospital for a few hours. The study was published online August 20 in Science Translational Medicine.
When studying gastric cancer, it was observed that there was a significant accumulation of nerves within the tumor microenvironment, and the density of the nerves seemed to correlate with prognosis, in the same way that blood vessels might be important to tumor growth.
The vagus nerve branches into 2 separate trunks in the stomach, each innervating half of it. The investigators found that cutting both branches of the vagus nerve really blocked the development of gastric cancer in mouse models, whereas cutting only one branch prevented tumor growth on one side of the stomach but not the other— indicating that this was a very local effect
The investigators found that denervation of the vagus nerve with localized botulinum toxin injections was as effective as vagotomy for blocking the development and progression of early and later stages of gastric cancer. Botulinum toxin blocks the release of all neurotransmitters, including acetylcholine, so that nerve endings can no longer communicate with other nerves or, in this case, the cancer stems cells that are driving cancerous growth. Subsequent experiments in the same mouse models showed that denervation with botulinum toxin injections could enhance the effect of systemic chemotherapy, and could enhance survival even in mice with advanced tumors. Loss of nervous input appears to make cancer cells more vulnerable to chemotherapy, which makes chemotherapy more efficient.
This research could have applications in other tumor types. The nerve–tumor growth connection is likely to be true in other solid tumors, such as in prostate cancer. Results in animal models have been so positive that a phase 2 clinical trial is underway in Norway, where patients with inoperable stomach cancer will receive injections of botulinum toxin in an effort to denervate the stomach and stop tumor progression.
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