A protein signal may explain why a breast cancer drug stops working
Original title: Targetable S100-RAGE signaling mediates intrinsic trastuzumab deruxtecan resistance in metastatic breast cancer.
How far along is this research?
- Lab cells
- Animals
- Review
- Tested in people
This was done in animals, not people. Most findings at this stage never become treatments.
The drug combination was only tested in cells and in animals, not in people.
The short version
Scientists found a possible reason why the drug T-DXd does not help some people, and a way to block it in lab and animal tests.
What was studied. Researchers studied 109 spots of spread breast cancer from people treated with the drug T-DXd. They compared tumor samples from people the drug helped with samples from people whose cancer grew right away. Then they tested a blocking drug in cancer cells and in animals.
What they found. The usual tumor lab tests did not show who would respond to T-DXd. In tumors that resisted the drug, a group of proteins called S100 was higher, and these switched on a survival signal through a protein called RAGE. When researchers blocked RAGE with a drug called TTP488, cancer cells started responding to T-DXd again, and animals with spread to the lung and brain had less cancer.
What this means, and what it doesn't
What it could mean: This points to one reason the drug may fail for some people. It also points to a possible way to fix that, by adding a second drug. Doctors cannot offer this combination today. It has not been tested in people yet.
What it doesn't mean: This does not mean there is a new treatment you can ask for. The tumor samples came from people, but the combination of the two drugs was only tested in cells in a dish and in animals. Results in animals often do not hold up in people. Human trials would need to happen first, and that takes years. This is not a cure, and it is not a promise that anyone will live longer.
Source: PubMed, July 17, 2026 · Read the original
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