Radiation Therapy Might Promote Amphiregulin, Enhancing Metastatic Growth

Recent research published in the journal Nature reveals that radiation therapy, commonly used to treat advanced solid tumors, can inadvertently stimulate the production of a molecule called amphiregulin, which is an epidermal growth factor receptor (EGFR) ligand. This molecule has been found to promote the growth of existing metastases, potentially worsening patient outcomes.

A study led by Dr. András Piffkó from the University of Chicago examined gene expression in biopsies taken before and after radiotherapy in patients with metastatic tumors. The findings demonstrated that radiation induces the tumor cells to produce amphiregulin. This reprograms EGFR-expressing myeloid cells into an immunosuppressive state, which diminishes their ability to combat tumor spread through processes like phagocytosis.

Furthermore, amphiregulin was identified as a key factor linked to increased metastatic tumor size and number. In clinical observations, patients with higher tumor levels of amphiregulin experienced shorter progression-free and overall survival times. Experimental models confirmed that while local radiotherapy could reduce the number of lung metastases, it also contributed to their growth by secreting amphiregulin.

Interestingly, blocking amphiregulin prevented this adverse effect in mouse models, leading to decreased tumor size and fewer metastatic sites. Combining radiation therapy with amphiregulin blockade showed promising results in reducing tumor progression, suggesting a potential new therapeutic approach.

This research underscores the complex interplay between radiation treatment and tumor biology, highlighting the importance of developing strategies to counteract the unintended promotion of metastases through molecules like amphiregulin.