A recent study conducted by the University of Chicago Medicine Comprehensive Cancer Center suggests that radiation therapy might contribute to the growth of untreated metastatic tumors, even those located far from the treatment site. This finding contrasts with the well-known "abscopal effect," where radiation to one tumor leads to shrinkage in others.
The research team observed an increase in untreated metastatic tumors when high dose radiation was applied, a phenomenon they termed the "badscopal effect." They attribute this reaction to heightened production of amphiregulin, a protein that weakens immune response and enhances cancer cell defense mechanisms.
Senior author Ralph Weichselbaum noted, “Our lab postulated that high doses of radiation might actually promote tumor growth at unirradiated sites under certain conditions, potentially accounting for some of these failures.” He added that historical studies suggested radiation could cause tumor spread, though it is generally seen as an effective anti-cancer agent within treated areas.
The study involved analyzing biopsy samples from a clinical trial led by Prof. Steven Chmura. It revealed that tumors at preexisting metastatic sites increased in size following Stereotactic Body Radiotherapy (SBRT). Further investigation by András Piffkó and his team found significant increases in amphiregulin levels in radiated tumors.
Blocking amphiregulin using antibodies or CRISPR technology resulted in shrinking tumors outside the radiation field. “Interestingly, the combination of radiation and amphiregulin blockade decreased both tumor size and the number of metastatic sites,” Weichselbaum stated.
In another trial led by Chmura, researchers linked failure to decrease amphiregulin after SBRT with worse outcomes. The study also highlighted how immune suppression correlates with cancer spread and death.
Collaborating with Assoc. Prof. Ronald Rock, researchers discovered that both amphiregulin and radiation elevated CD47 levels—a signal aiding tumor cells in evading immune detection. Blocking both molecules alongside radiotherapy effectively controlled metastatic tumors in animal models.
“These results open a whole new way of thinking about the systemic effects of radiotherapy,” Weichselbaum said. Plans for a clinical trial are underway to further explore these findings.
The study titled “Radiation-induced amphiregulin drives tumor metastasis” received support from several institutions including the National Cancer Institute and Ludwig Foundation.