Radiation therapy can promote amphiregulin, which increases growth of metastases

Radiation therapy can promote the epidermal growth factor receptor (EGFR) ligand amphiregulin, which increases growth of existing metastases in patients with advanced solid tumors, according to a study recently published online in Nature.

András Piffkó, M.D., from the University of Chicago, and colleagues explored the potentially deleterious effect of radiation in promoting metastasis in patients with advanced solid tumors who received stereotactic body radiotherapy to multiple metastatic sites. Gene expression was examined in 22 matched preradiotherapy and postradiotherapy biopsies for irradiated metastases.

The researchers found that the EGFR ligand amphiregulin was induced by radiotherapy in tumor cells; amphiregulin reprograms EGFR-expressing myeloid cells toward an immunosuppressive phenotype and can reduce phagocytosis. Amphiregulin was involved in three of the top 20 upregulated gene pathways correlating with distant tumor progression. Patients whose tumors expressed increased amphiregulin had shorter progression-free and overall survival. Local radiotherapy reduced the number of lung metastases but increased their size via secretion of amphiregulin; gene knockout prevented this effect. Similar findings were seen in mouse lung metastasis models and were overcome by a blockade of amphiregulin.

“Interestingly, the combination of radiation and amphiregulin blockade decreased both tumor size and the number of metastatic sites,” senior author Ralph R. Weichselbaum, M.D., also from the University of Chicago, said in a statement.

Several authors disclosed ties to the biopharmaceutical industry.

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