The 'Badscopal Effect': High-Dose Radiation Therapy May Promote Growth in Untreated Distant Tumors

Recent research from the University of Chicago Medical Center has unveiled a surprising phenomenon termed the 'badscopal effect,' where high doses of radiation therapy, contrary to expectations, can stimulate growth in metastatic tumors that are not directly targeted by the treatment. Traditionally, radiotherapy is known to shrink tumors locally and sometimes induce the abscopal effect, where tumors at distant sites regress due to immune system activation. However, this new study highlights a paradoxical response.

The researchers observed that in some cases, high-dose radiation enhances the production of amphiregulin, a protein that activates cellular pathways involved in survival, proliferation, and migration of cancer cells. Increased amphiregulin not only aids tumor cells in resisting immune attacks but also promotes the growth of existing metastases. Gene expression profiling of patient samples before and after radiotherapy revealed that the gene encoding amphiregulin was significantly upregulated post-treatment.

Animal models of lung and breast cancer confirmed these findings, showing that radiation decreased the emergence of new metastatic sites but inadvertently stimulated the growth of pre-existing metastases. Importantly, blocking amphiregulin with antibodies or gene editing techniques reduced tumor growth outside the radiation field. Furthermore, combining amphiregulin and CD47 blockade with radiotherapy resulted in better control of metastatic spread.

The study also explored the immune suppressive environment fostered by amphiregulin. Elevated levels of amphiregulin correlated with an increase in immunosuppressive myeloid cells and the upregulation of CD47, a molecule that signals immune cells not to engulf tumor cells. Inhibiting these pathways in animal models led to improved outcomes, suggesting potential personalized strategies to counteract the badscopal effect.

These findings challenge existing perceptions of radiotherapy’s systemic effects, indicating that, under certain conditions, radiotherapy may unintentionally promote metastatic tumor growth. The researchers emphasize the importance of integrating molecular inhibitors into treatment plans for metastatic cancer and are planning clinical trials to further validate these strategies. Overall, this research sheds light on the complex tumor-immune interactions post-radiation, paving the way for more effective, personalized cancer therapies.