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Radiation therapy may enhance metastasis growth via amphiregulin
Last reviewed: 15.07.2025
Radiation therapy may stimulate production of the epidermal growth factor receptor (EGFR) ligand amphiregulin, which promotes the growth of existing metastases in patients with advanced solid tumors, according to a study recently published online in the journal Nature.
András Piffkó, MD, of the University of Chicago, and colleagues studied the potential harmful effects of metastatic-promoting radiation therapy in patients with advanced solid tumors who were treated with stereotactic body radiation therapy (SBRT) to multiple metastatic sites. Gene expression was analyzed in 22 paired metastatic biopsies before and after radiation therapy.
The scientists found that radiation therapy induced the production of amphiregulin in tumor cells. Amphiregulin reprograms myeloid cells expressing EGFR to an immunosuppressive phenotype and can reduce their phagocytic activity. Amphiregulin was involved in three of the twenty most activated signaling pathways associated with the progression of distant tumors. Patients whose tumors showed increased expression of amphiregulin had shorter disease-free and overall survival.
Local radiotherapy reduced the number of lung metastases but increased their size due to secretion of amphiregulin; gene knockout prevented this effect. Similar results were obtained in mouse models of lung metastases, where blockade of amphiregulin abolished this effect.
"Interestingly, the combination of radiation therapy and amphiregulin blockade reduced both tumor size and the number of metastatic sites," noted senior author Ralph R. Weichselbaum, MD, also of the University of Chicago.
Several study authors reported ties to the biopharmaceutical industry.