In mice, blocking BDNF signalling with an existing drug kept nerves out of triple-negative breast tumours and reduced their growth.
Tumours are not just masses of dividing cells. They recruit what they need from the surrounding tissue — blood vessels, structural cells, immune cells — and in recent years nerves have joined that list. Nerve fibres grow into tumours, and in several cancers the density of that innervation predicts worse outcomes.
A study in Cell Death and Differentiation from the University of Oklahoma identifies where the recruiting signal comes from in triple-negative breast cancer, and the answer is the immune system.
Macrophages inside the tumour release brain-derived neurotrophic factor, or BDNF, which draws nearby nerves in. BDNF is best known for its role in nerve growth and plasticity in the brain; the finding is that breast tumours appear to hijack it.
“Macrophages are the critical source for drawing nerves into the tumor,” said Maureen Cox, an assistant professor in the Department of Microbiology and Immunology at the OU College of Medicine and a research member of OU Health Stephenson Cancer Center.
An immune cell working for the tumour
The irony in the result is the part worth dwelling on. Macrophages are the immune system’s first responders, cells that normally consume pathogens and coordinate wound repair, and tumours routinely recruit them in large numbers and then repurpose them.
This is well established in outline: tumour-associated macrophages are generally pushed toward a wound-healing phenotype, in which they promote blood vessel growth, remodel tissue and suppress the immune response rather than attack the tumour. A tumour is in some sense a wound that does not heal, and the macrophages behave accordingly.
Axon growth fits that pattern. Pulling nerve fibres into damaged tissue is part of repairing it, and BDNF is one of the signals that does so. The tumour is making use of a repair programme that the macrophages already have.
What the nerves are thought to do
Why nerve ingrowth would help a tumour is the question the work points at rather than answers, and Cox’s hypothesis is immunological.
“We believe that the nerves are immunosuppressive, so if we can stop the nerves from growing in the first place,” she said — the implication being that the tumour’s immune defences would be weakened along with them.
There is a basis for that idea in the wider literature. Nerve endings release neurotransmitters and neuropeptides that act on immune cells, and several of those signals dampen T-cell activity. A tumour that recruits nerves may be arranging a local supply of immunosuppressive signalling, which would make innervation a defence mechanism rather than a side effect.
It is a hypothesis. The study establishes that macrophage-derived BDNF brings nerves in and that blocking it reduces tumour growth; whether the growth reduction works through restored immunity, through some other effect of denervation, or through BDNF acting on the tumour cells directly is not something the release distinguishes.
The drug, and the care it needs
In mice, a drug already on the market that blocks BDNF signalling stopped nerves infiltrating the tumour and significantly reduced its growth.
“It looks really promising that we can use this drug, which is already on the market, to target BDNF,” Cox said.
An existing approved drug is genuinely a shortcut, because its safety profile and pharmacology are known and repurposing trials can start from a much better position than a new molecule. It is also where this result needs the firmest caveats, and the release supplies none.
The drug is not named. The experiments are in mice, and mouse tumour models have an extensive record of promising results in breast cancer that did not survive contact with patients. No dose, no treatment schedule, no survival data and no numbers of any kind are reported — the release contains not a single quantitative result, which for a paper reporting a significant reduction in tumour growth is a notable omission.
Nothing here is a reason for anyone with breast cancer to seek out a BDNF inhibitor, and the absence of a drug name makes that the only sensible reading in any case.
The human data
The patient-level evidence is associative. In data from people with triple-negative breast cancer, tumours with higher macrophage and BDNF levels were associated with poorer survival.
That is the right check to run and it carries the limits of its design. Macrophage infiltration is already known to predict worse outcomes in breast cancer, so a correlation between macrophage-rich tumours and poor survival does not by itself implicate BDNF or the nerves; it is consistent with the mechanism rather than evidence of it.
Triple-negative breast cancer is the right disease to look at. It lacks the oestrogen, progesterone and HER2 receptors that the main targeted therapies act on, which leaves chemotherapy and a narrow set of immunotherapies, and it is more common in younger women and in Black women. A mechanism that reaches it through the immune microenvironment rather than through a receptor is worth pursuing for that reason alone.
Where it goes
Cox’s group plans to examine whether the nerves promote blood vessel growth and whether tumour cells use nerves as a route to metastasise — the second being the more consequential question, since nerve tracts are a plausible physical pathway out of a tumour and perineural invasion is already a recognised route of spread in other cancers. She also intends to test the approach in high-grade ovarian cancer.
“Ultimately, we want to turn the anti-tumor immunity back on in cancer patients,” Cox said.
The work was supported by the National Institute of General Medical Sciences at the NIH (P20GM103447 and P20GM103639), Oklahoma’s Tobacco Settlement Endowment Trust, and Oklahoma Shared Clinical and Translational Resources through an NIGMS Institutional Development Award (U54GM104938). The paper was published on 2 July 2026; the release does not give the full author list or state any conflicts of interest.
Notes
- Cell Death and Differentiation, 2026. DOI: 10.1038/s41418-026-01796-5. The release does not give the full paper title or author list.
- University of Oklahoma. “Researchers discover how tumors enlist nerves to keep growing.” EurekAlert!, 4 August 2026. https://www.eurekalert.org/news-releases/1138779.
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