Lung cancer plugs into the mouse brain

Recent research published on September 10 in Nature highlights a significant discovery regarding the intricate relationship between lung cancer and the brain. The study shows that once lung cancer cells infiltrate the brain, they can integrate into the brain’s electrical circuits, leading to their growth.

Neuroimmunologist Sebastien Talbot from Queen’s University in Kingston, Canada, praised the findings, stating, “It’s remarkable work. Observing how these tumors are reprogrammed is fascinating, especially how they establish electrical connections with brain neurons.”

Small-cell lung cancer (SCLC) is notably aggressive and typically originates in the lungs before spreading to the brain, often resulting in dire implications for patient health. “Metastasis is a turning point for patients, leading to a significant decline in their condition,” explained coauthor Humsa Venkatesh, a cancer neuroscientist at Brigham and Women’s Hospital and Harvard Medical School. “Currently, there are limited treatment options for these metastases.”

The team aims to deepen understanding of how the nervous system interacts with cancer cells, potentially paving the way for breakthroughs in cancer treatment through the targeting of nerve cell activity.

Venkatesh noted that the nervous system’s involvement extends across various cancers beyond lung cancer. “Regardless of the type of cancer—breast, skin, gastric, or pancreatic—the presence of nerves in the tumor microenvironment plays a role in influencing tumor growth,” she observed.

In the study, the researchers conducted experiments on mice with SCLC. They discovered that severing the vagus nerve, which transmits signals between the brain and body, significantly hindered cancer growth within the lungs. “The results were some of the most profound I’ve encountered,” Venkatesh remarked, “Clipping that nerve essentially stopped tumor growth.”

The researchers proceeded to simulate metastasis by injecting lung cancer cells into the brains of the mice. Observations through high-powered microscopy revealed that the resultant brain tumors were intertwined with neurons. Surprisingly, these neurons formed synaptic connections with the cancer cells, facilitating the transmission of growth signals that prompted the cancer cells’ proliferation.

Neuroscientist and neuro-oncologist Michelle Monje, a coauthor and Howard Hughes Medical Institute investigator at Stanford University, underscored the parasitic characteristics of cancer. “Cancers seldom create new mechanisms; rather, they exploit and hijack existing biological processes,” she explained.

An additional study that was also published in Nature on the same day supports the notion that the interactions between neurons and tumor cells are crucial. The findings indicated that genetic alterations affecting synapse formation and neural communication may contribute to the growth of small-cell lung cancer.

The researchers also tested the effects of levetiracetam, an epilepsy medication known to reduce neuronal electrical activity, on the tumor’s growth in the brains of the mice. The drug was found to inhibit cancer cell proliferation, suggesting that other pharmaceuticals or devices aimed at lowering neural activity might present new avenues for tackling cancer metastasis. Venkatesh expressed optimism about future efforts, stating, “We’re at the very beginning of this exploration,” though she acknowledged the journey ahead is still long.