Radiation therapy is often seen as a powerful weapon against cancer.
But a surprising new study from the University of Chicago Medicine shows that, under certain conditions, high doses of radiation might actually make cancer worse by helping tumors spread.
The researchers have dubbed this unexpected reaction the “badscopal effect”—a play on the well-known “abscopal effect,” where radiation to one tumor leads to shrinkage of tumors in other parts of the body.
The research, led by Professor Ralph Weichselbaum and his team, focused on a protein called amphiregulin.
When high doses of radiation were used to treat a tumor, the treated cancer cells began producing more amphiregulin.
This protein seems to interfere with the body’s immune system, helping cancer cells grow and spread more easily—even in areas that weren’t directly treated with radiation.
In the study, patients received a type of high-dose radiation called Stereotactic Body Radiotherapy (SBRT), sometimes combined with immunotherapy.
Surprisingly, the researchers noticed that in some patients, existing tumors outside the treatment area began to grow faster after radiation.
To understand why this was happening, the team looked at tumor samples before and after treatment.
They found that radiation increased amphiregulin levels, which in turn activated cell signals that help tumors survive and grow.
The same pattern was confirmed in mouse models of lung and breast cancer. Although radiation reduced the number of new cancer sites, it made the existing ones grow larger.
However, when the researchers blocked amphiregulin using special antibodies or gene-editing tools like CRISPR, tumors outside the radiation zone began to shrink. This suggested that targeting amphiregulin could prevent radiation from helping cancer spread.
Even more powerful results came when they combined radiation with treatments that blocked both amphiregulin and another protein called CD47. CD47 sends a “don’t eat me” signal to immune cells, helping tumors hide from the body’s defenses. Blocking both proteins allowed immune cells to attack the cancer more effectively.
Further tests showed that when amphiregulin levels remained high after radiation, patients tended to do worse, with more tumor growth and lower survival. These cases also showed an increase in immune cells that suppress the body’s ability to fight cancer. This shows that amphiregulin not only fuels tumor growth but also weakens the immune response.
The researchers now plan to launch clinical trials to test new therapies that target these molecules. Their goal is to make radiation therapy safer and more effective for people with metastatic cancer by stopping the harmful side effects it can sometimes trigger.
According to Weichselbaum, the findings may change how doctors think about radiation’s impact on the whole body—not just the area being treated.
