Researchers uncover key to overcoming drug resistance in breast cancer

Researchers in China have identified sensory nerves within tumors as a primary cause of immunotherapy resistance in patients with triple-negative breast cancer, a discovery that could lead to more effective treatments using existing migraine medication.

The study, published on Friday in the journal Cell, suggests that these nerves act as "commanders" that block the body's immune system from attacking the cancer.

Triple-negative breast cancer, or TNBC, is often called the most dangerous form of the disease. It accounts for nearly one-fifth of all breast cancer cases and is known for being highly aggressive, with a high risk of spreading to other parts of the body within five years.

While modern treatments like immunotherapy—which uses the body's own immune system to fight disease—have offered hope, many patients do not respond to them or develop resistance quickly.

The research team, consisting of experts from Fudan University Shanghai Cancer Center and the Institute for Translational Brain Research of Fudan University, shifted their focus away from just the cancer cells themselves. Instead, they looked at the "environment" around the tumor.

After analyzing 360 clinical samples, the team found that tumors heavily invaded by sensory nerves—the same nerves responsible for touch and pain—had the worst outcomes.

"We found that these sensory nerves prevent immune cells from penetrating core areas within the tumor," said Shao Zhimin, a lead researcher and director of general surgery at the center.

The study found that tumor cells send signals to these nerves. The nerves then trigger nearby cells to produce a thick layer of collagen.

This creates a physical barrier, essentially building a wall that keeps immune treatments from reaching the cancer cells, said Jiang Yizhou, another lead expert on the team.

To test how to break this barrier, the researchers used rimegepant, a drug already approved and widely used to treat migraines.

In animal models, using the migraine medication to block nerve signals not only slowed the cancer's growth but also helped immunotherapy drugs work more effectively. Because rimegepant is already an established drug, experts believe these findings could be transitioned to clinical use for cancer patients relatively quickly.

Shao said the research demonstrates the importance of viewing the nervous system and the immune system as an integrated whole when treating cancer.