Botox may be useful in treating stomach cancers

“Botox may have cancer fighting role,” BBC News reports after research involving mice found using Botox to block nerve signals to the stomach may help slow the growth of stomach cancers. Botox, short for botulinum toxin, is a powerful neurotoxin that can block nerve signals.

The researchers studied genetically modified mice designed to develop stomach cancer as they grew older.

They found that mice treated with Botox injections had improved survival rates, because the cancer spread at a reduced rate or was prevented from developing in the first place.

Cutting the nerve supply to the stomach during an operation called a vagotomy had a similar effect.

In mice that had already developed stomach cancer, Botox injections reduced cancer growth and improved survival rates when combined with chemotherapy.

Further studies of human stomach cancer samples confirmed the finding that nerves play a role in tumour growth.

An early-phase human trial is now underway in Norway to determine the safety of such a procedure and to work out how many people would need to be treated in trials, to see whether the treatment is effective.

Where did the story come from?

The study was carried out by researchers from the Norwegian University of Science and Technology in Trondheim, Columbia University College of Physicians and Surgeons in New York, and universities and institutes of technology in Boston, Germany and Japan.

It was funded by the Research Council of Norway, the Norwegian University of Science and Technology, St Olav’s University Hospital, the Central Norway Regional Health Authority, the US National Institutes of Health, the Clyde Wu Family Foundation, the Mitsukoshi Health and Welfare Foundation, the Japan Society for the Promotion of Science Postdoctoral Fellowships for Research Abroad, the Uehara Memorial Foundation, the European Union Seventh Framework Programme, the Max Eder Program of the Deutsche Krebshilfe and the German Research Foundation.

The study was published in the peer-reviewed medical journal Science Translational Medicine.

The study was reported accurately by the UK media, making it clear that this potential treatment is not yet available and will take years to assess its potential.

What kind of research was this?

This research was a collection of experiments on mice and studies of human tissue samples. Previous research had shown that cutting the main nerve to the stomach (vagus) in a procedure called a vagotomy reduces the thickness of the stomach wall and decreases cell division.

Another research study found people who had a vagotomy had a 50% reduced risk of developing stomach cancer 10 to 20 years later. The researchers wanted to see if targeting the nerve would reduce stomach cancer growth.

What did the research involve?

Genetically modified mice designed to develop stomach cancer by 12 months of age were studied to see if there was a link between the density of nerves and stomach cancer.

One of four different types of operation was then performed on the vagus nerve of 107 genetically modified mice at the age of six months to see if this made a difference in the development of stomach cancer. This was either:

• a sham operation
• pyloroplasty (PP) – surgery to widen the valve at the bottom of the stomach so the stomach can empty food more easily
• bilateral vagotomy with pyloroplasty (VTPP) – cutting both sections of the vagus nerve and widening the valve
• anterior unilateral vagotomy (UVT) – cutting just the front section of the vagus nerve

The researchers then performed a Botox procedure on another set of mice by injecting the anterior vagus nerve (front section) when they were six months old to see if this reduced the development of stomach cancer.

To see if cutting or injecting the nerve had any effect after stomach cancer had developed, the researchers performed UVT on mice aged 8, 10 or 12 months and compared their survival rate with mice who had not had the intervention.

They then injected Botox into the stomach cancer of mice aged 12 months and looked at the subsequent cancer growth. They also compared survival rates for chemotherapy with saline injection, chemotherapy with Botox and chemotherapy with UVT.

The researchers then examined human stomach samples from 137 people who had undergone an operation for stomach cancer, to look at how active the nerves were in the sections of cancer compared with normal tissue.

They also compared tissue samples of 37 people who had already had an operation for stomach cancer, but then developed stomach cancer in the base portion of the stomach. The vagus nerve had been cut in 13 of these people.

What were the basic results?

The genetically modified mice mostly developed stomach cancer in the section of the stomach that had the highest density of nerves.

Cutting the vagus nerve supply reduced the incidence of tumours developing. The percentage of mice that had tumours six months after the operation was:

• 78% after the sham surgery
• 86% after PP
• 17% after VTPP
• 14% in the front section of the stomach (where the nerve had been cut) and 76% in the back section (where the vagus nerve was still intact) after UVT

Six months after the Botox injection into the anterior vagus nerve, the mice still developed stomach cancer. However, the size of the tumour and number of dividing cancer cells in the front section of the stomach was less than half that of the back section.

In mice that had already developed stomach cancer, the normal survival rate was 53% by 18 months, but this was increased by the UVT to:

• 71% if the UVT was performed at 8 months
• 64% if the UVT was performed at 10 months
• 67% if the UVT was performed at 12 months

Botox injection into the stomach tumours of mice reduced the growth by roughly half. Botox and chemotherapy improved mouse survival compared with chemotherapy on its own, as did UVT and chemotherapy.

In the human samples, there was evidence of increased nerve activity in the cancer sections of tissue compared with the normal tissues. This was higher in more advanced tumours.

All 24 people who had not had the vagus nerve cut developed stomach cancer in the base, as well as the remaining front and back sections of the stomach. Only one of the 13 people who had had the vagus nerve cut developed cancer in the front or back section of the stomach, suggesting that the nerve needed to be intact for cancer to develop.

How did the researchers interpret the results?

The researchers say that their “finding that nerves play an important role in cancer initiation and progression highlights a component of the tumour microenvironment contributing to the cancer stem cell niche.

“The data strongly supports the notion that denervation and cholinergic antagonism, in combination with other therapies, could represent a viable approach for the treatment of gastric cancer and possibly other solid malignancies.”

Conclusion

These laboratory experiments show that nerves have a role in the development and advancement of stomach cancer. The early experiments in mice found that stopping the nervous supply by either cutting the vagus nerve or injecting it with Botox improved survival rates and reduced cancer growth.

The Botox injections were not performed on any humans in this study. However, an early-phase clinical trial in humans with inoperable stomach cancer began in Norway in January 2013, with the results expected in 2016.

This will determine the safety of such a procedure and work out the number of people who would need to be treated in a larger controlled trial to see whether the treatment is effective.

You can reduce your risk of stomach cancer by quitting smoking if you smoke and moderating your consumption of salt and smoked meats, such as pastrami.

Stomach cancer has also been linked to a chronic infection by H. pylori bacteria, a common cause of stomach ulcers.

If you find yourself having persistent bouts of indigestion or stomach pain, you should contact your GP for advice. The symptoms could be caused by a H. pylori infection, which is relatively straightforward to treat.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Links To The Headlines

Botox may have cancer fighting role. BBC News, August 21 2014

Botox could be used as new treatment for stomach cancer as scientists discover anti-wrinkle treatment slows tumour growth. Daily Mail, August 21 2014

Botox ‘could be used to treat stomach cancer’. Daily Mirror, August 21 2014

Botox could halt stomach cancer. The Daily Telegraph, August 21 2014

Links To Science

Zhao C, Hayakawa Y, Kodama Y, et al. Denervation suppresses gastric tumorigenesis. Science Translational Medicine. Published online August 20 2014