Researchers from Columbia University Medical Center found that nerves play a critical role in stomach cancer growth and blocking nerve signals using surgery or Botox (onabotulinumtoxinA) could be an effective treatment for the disease.
“Scientists have long observed that human and mouse cancers contain a lot of nerves in and around the tumour cells,” said Dr Timothy C Wang, the Dorothy L and Daniel H Silberberg Professor of Medicine at Columbia’s Herbert Irving Comprehensive Cancer Center.
“We wanted to understand more about the role of nerves in the initiation and growth of cancer, by focusing on stomach cancer,” Wang added.
Using three different mouse models of stomach cancer, Wang’s team found that when they performed a procedure called a vagotomy to cut the nerves, the surgery significantly slowed tumour growth and increased survival rates.
Removing nerve connections from only one side of the stomach allowed cancer to continue growing on the other side (with the intact nerves), providing further evidence of the importance of nerves in tumour growth.
Wang’s team then tried to block transmission of nerve signals pharmacologically. They found that when they injected Botox into mice, the drug proved to be as effective as surgery at reducing stomach cancer growth.
“We found that blocking the nerve signals makes the cancer cells more vulnerable – it removes one of the key factors that regulate their growth,” said Wang.
Botox prevents nerve cells from releasing a neurotransmitter called acetylcholine. In the case of cosmetic treatment, for example, blocking acetylcholine helps to lessen facial wrinkles by causing temporary paralysis of the muscles.
Because acetylcholine also ordinarily stimulates cell division, using Botox to prevent acetylcholine release might help slow the growth of cancer.
Wang’s team also found evidence of the effectiveness of targeting nerves for cancer treatment in human patients when they compared 37 patients who had a recurrence of stomach cancer many years after surgery.
Of the 13 patients who had had a vagotomy as part of their procedure, in all but one case, tumours did not develop in regions where the nerve connections had been severed.
By contrast, tumours were found in the same region of the stomach in all 24 patients who had not had a vagotomy.
Next, Wang’s team plans to investigate the effectiveness of nerve-targeted therapy used in combination with other cancer treatments.
Initial experiments have shown that blocking nerves makes cancer cells more vulnerable to chemical
agents. Botox used in combination with chemotherapy in mice increases survival rates up to 35 per cent, compared with chemotherapy alone.
The study is published in the journal Science Translational Medicine.