Targeting nerves and their connections could potentially shrink stomach cancers

New research from Columbia University Medical Center (NY, USA) has highlighted the role that nerves play in stomach cancer growth. Thomas C Wang (Columbia University College), in collaboration with Duan Chen (Norwegian University of Science and Technology, Norway), demonstrated that severing nerves surgically or blocking nerve signals pharmacologically through the use of Botox® could reduce growth of stomach cancers. The research was published recently in Science Translational Medicine.

“Scientists have long observed that human and mouse cancers contain a lot of nerves in and around the tumor cells,” explained Wang (Columbia University College). “We wanted to understand more about the role of nerves in the initiation and growth of cancer, by focusing on stomach cancer.”

The researchers investigated three different mouse models of stomach cancer, observing that a vagotomy both slowed growth of tumors and increased the rate of survival. Furthermore, they carried out investigations involving removing nerves only on one side of the stomach, while the nerves on the other side remained intact. Here the researchers observed that the cancer only continued to grow on the side where the nerves remained intact.

Similar results were observed when nerve signals were blocked pharmacologically with Botox. “We found that blocking the nerve signals makes the cancer cells more vulnerable—it removes one of the key factors that regulate their growth,” continued Wang.

Wang also looked at the effects of vagotomy in 37 patients who had a reoccurrence of stomach cancer, years after surgery. Of the 13 patients who underwent a vagotomy, in all but one he found that the stomach cancer did not redevelop in the region of the vagotomy. This differed from the 24 who had not undergone a vagotomy, in whom he found that all patients developed tumors in the same regions of the stomach.

The team now plans to investigate the effectiveness of the nerve-targeted therapy alongside other cancer treatments. His team have previously demonstrated that blocking nerve signals increases the susceptibility of the tumors to chemical treatments. In mice they found that when Botox was used in conjunction with chemotherapy, survival rates increased by 35% in comparison to the use of Botox only.

The researchers recognize the limitations of their work, acknowledging that their research primarily focused on the early stages of stomach cancer. “In the future, we’d really like to look at how we can use this method of targeting nerves to stop the growth of more advanced tumors,” Wang concluded. His team now hope to develop drugs that block neurotransmitter receptors, as they believe that it will enable them to reach cells that have metastasized.

Source: Zhao CM, Hayakawa Y, Kodama Y et al. Denervation suppresses gastric tumorigenesis. Sci Transl Med. doi: 10.1126/scitranslmed.3009569 (2014); Columbia University Medical Centre press release