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The dark side of radiotherapy
András Piffkó1, Sean P Pitroda2, Ralph R Weichselbaum2
1Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL, USA; The Ludwig Center for Metastasis Research, University of Chicago, Chicago, IL, USA; Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Cancer Cell
|July 4, 2025
Summary
Radiotherapy may paradoxically enhance cancer metastasis via growth factors and immune changes, particularly through amphiregulin-epidermal growth factor receptor (EGFR) signaling. Targeting myeloid cells and EGFR pathways is crucial for mitigating these pro-metastatic effects.
Area of Science:
- Oncology
- Cancer Research
- Immunology
Background:
- Radiotherapy (RT) is a cornerstone of cancer treatment.
- Paradoxically, RT can promote cancer metastasis through systemic effects.
- Amphiregulin-epidermal growth factor receptor (EGFR) signaling is implicated in RT-induced metastasis.
Purpose of the Study:
- To investigate the pro-metastatic effects of radiotherapy.
- To elucidate the role of RT-induced growth factors and immune modulation in metastasis.
- To explore therapeutic strategies targeting myeloid cells and EGFR pathways to counteract RT-induced metastasis.
Main Methods:
- Analysis of emerging evidence on RT-induced systemic effects.
- Focus on amphiregulin-epidermal growth factor receptor (EGFR) signaling pathways.
- Review of therapeutic approaches targeting myeloid cells and EGFR.
Main Results:
- Radiotherapy can induce growth factors and immune modulation.
- Amphiregulin-EGFR signaling plays a key role in facilitating metastatic outgrowth.
- These mechanisms contribute to the pro-metastatic consequences of RT.
Conclusions:
- Refining RT strategies is essential to mitigate pro-metastatic effects.
- Identifying high-risk patients for metastasis is crucial.
- Therapeutic combinations targeting myeloid cells and EGFR pathways show promise for optimizing cancer treatment outcomes, especially in the immunotherapy era.
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