Radiotherapy for brain metastasis can later cause neurocognitive decline. Sometimes this is a tradeoff when fighting brain cancer, but when patients don’t respond to radiation therapy, they experience this side effect of radiotherapy without any benefit. In a study published in Nature Medicine, researchers say they've found a way to predict who is most likely to be resistant to whole brain radiotherapy (WBRT) for brain metastasis.
The Spanish research team that published the study looked at mouse models and brain metastasis organotypic cultures from patients with radiotherapy resistance to examine factors involved in radiation therapy resistance. Patients who are said to be resistant to radiotherapy are those with tumor progression and recurrence of metastatic lesions despite receiving radiation.
Cancer metastasizes to the brain in anywhere from 20% to 40% of patients with solid tumors, usually in patients with lung cancer, breast cancer, or melanoma. While treatment of these metastases is shifting more towards targeted stereotactic radiosurgery, WBRT continues to be an important treatment option for these patients.
Researchers from the study state the blood biomarker S100A9 may indicate if a patient will respond to WBRT. S100A9 is secreted by brain metastases. Activation of the S100A9-RAGE-NF-kB-JunB pathway in these metastases is thought to be a potential pathway of resistance to radiation treatments.
Manuel Valiente, PhD, the study's lead author, states, "I did not expect it to be that simple," in commenting on how easy it was to detect S100A9 in the blood. "But there is a correlation between the levels of S100A9 in the blood of patients and their resistance to radiotherapy."
From blood samples taken from 71 patients with brain metastases who had received WBRT, higher S100A9 levels in the blood were associated with poorer response to radiation treatments.
However, in the study's experimental models, the researchers also showed there is a way to restore sensitivity to radiation – through RAGE inhibitor FPS-ZM1. The authors suggest that concurrent use of RAGE inhibitors with WBRT may also minimize radiation side effects on normal brain tissue by lowering the amount of radiation needed to kill cancer cells.