NYC Gazette

Researchers at Columbia University Vagelos College of Physicians and Surgeons have discovered that stomach cancers in mice establish electrical connections with nearby sensory nerves, stimulating the cancer's growth and spread. This finding, published on February 19 in Nature, is significant as it is the first time such electrical contacts between nerves and a cancer outside the brain have been identified.

Timothy Wang, leading the study, noted, "We know that many cancers exploit nearby neurons to fuel their growth, but outside of cancers in the brain, these interactions have been attributed to the secretion of growth factors broadly or through indirect effects." He added that this discovery raises possibilities for repurposing neurological drugs for cancer treatment.

The research focused on how sensory neurons react to stomach cancer. In experiments with mice, some sensory neurons extended into tumors due to a protein called Nerve Growth Factor (NGF) released by cancer cells. The tumors then signaled these nerves to release Calcitonin Gene Related Peptide (CGRP), which induced electrical signals within the tumor.

Wang explained that while classical synapses may not form where neurons meet cancer cells, "there’s no doubt that the neurons create an electric circuit with the cancer cells." Using calcium imaging techniques confirmed this electrical activity.

This neural-cancer connection forms a feedback loop: "There’s a circuit that starts from the tumor, goes up toward the brain, and then turns back down toward the tumor again," Wang said. CGRP inhibitors currently used for migraines were shown in Wang's study to reduce tumor size and prevent spread when administered to mice with stomach cancer.

"Based on our analysis of stomach cancer data from patients," Wang continued, "we believe that circuits we’ve found in mice also exist in humans and targeting them could be an additional useful therapy."

Unpublished findings suggest sensory neurons might stimulate cancer indirectly through other pathways. For example, they may interact with connective tissue cells or cause T cell exhaustion impacting immune responses against other cancers. Nonetheless, according to Wang: "But we think it all starts with the cancer cell setting up a neural circuit."

The research was supported by grants from various NIH sources and involved contributions from multiple authors across different institutions including Columbia University and others abroad.