A common wrinkle busting agent could be useful in treating stomach cancers, a new study has found. Published in the journal Science Translational Medicine, Columbia University Medical Center researchers describe findings that suggest nerves play a role in facilitating stomach cancer growth and that inhibiting nerve signals through surgery or Botox could slow tumor growth.
Gastric cancer is the fifth most common cancer in the world and the second highest contributor to cancer mortality. The majority of stomach cancers seem to be triggered by infection with a bacterium called Helicobacter pylori that burrows into the mucus lining of the stomach, causing inflammation. This bug is found in around two-thirds of the global population, but only 1-2 out of every 100 infected develop stomach cancer. This suggests that there are other factors at play that contribute to the development of cancer- but what are they?
Recent evidence has highlighted the role of a signaling pathway called Wnt. This pathway involves the release of proteins called Wnts that regulate cell fate and migration, amongst other things. It seems that H. pylori is able to inappropriately switch on this pathway, leading to the activation of stomach stem cells which ultimately leads to cancer. However, it was evident that this wasn’t the full story, so this new research set out to fill in some of the blanks.
Previous observations suggested that nerves may play a role in cancer development. Furthermore, in patients with peptic ulcers, chopping a nerve that connects the stomach with the brain called the vagus nerve seemed to reduce the risk of developing stomach cancer. So, Colombia researchers decided to see if blocking signaling from this nerve could halt tumor growth.
The scientists started off by severing the vagus nerve connections in three different mouse models of cancer. They found that this significantly slowed tumor growth and increased survival rates. Furthermore, if they only chopped the connections on one side of the tumor, it continued to grow on the other side.
Taking this one step further, they administered the mice with Botox. Botox is a lethal toxin produced by the bacterium Clostridium botulinum. It’s used in small amounts in cosmetic procedures because it prevents nerve cells from releasing a neurotransmitter called acetylcholine, which temporarily paralyzes face muscles. This so-called cholinergic signaling seems to stimulate gastric cancer by activating the Wnt pathway via a receptor called M3.
After injecting the mice with Botox, the team found that tumor incidence and progression was significantly reduced. Furthermore, it seemed to enhance the effects of chemotherapy, suggesting this may be effective as a combination therapy.
Finally, to see if this is worth pursuing in patients, the researchers looked at human stomach cancer samples. They found that the more advanced the cancer, the more nerves the tumors seemed to have. Furthermore, some also displayed overactive Wnt signaling.
The researchers are certainly encouraged by these results, but a lot more work needs to be done. As an expert gastroenterologist pointed out to Cancer Research UK, none of the mouse models had cancers exclusively triggered by H. pylori. They also only had localized, early-stage cancers. While Botox may help primary tumors, it isn’t going to be able to tackle secondary cancers. However, there is light at the end of the tunnel, as their results seem to suggest a drug targeting the M3 neurotransmitter receptors may be effective, and one is already on the market.
[Via New Scientist, Columbia University, Science, and CRUK]