Radiation is one of the oldest and most common therapies for cancer, and typically is delivered locally, or to specific targeted sites in the body. While it has long been thought that locally-delivered radiation therapy typically does not help to shrink tumours outside the field of irradiation, new preclinical research from a team at Roswell Park Comprehensive Cancer Center suggests a strategy for significantly increasing both the local and distant, or “abscopal,” effects of radiation. Results of the study, which was led by Elizabeth Repasky, PhD, have been newly published in Nature Communications.
“Our work suggests that the benefits of radiation therapy, both on the target site and in tumours located elsewhere in the body, are directly related to the degree of stress an individual may be experiencing. In our laboratory studies, irradiated tumours went away faster when stress was reduced, and even distant tumours that did not receive radiation also shrunk or disappeared,” says Dr. Repasky, Cell Stress Program co-leader and William Huebsch Professor of Immunology at Roswell Park. “We have demonstrated even mild stress occurring over a longer period of time — not just singular moments, but chronic stress — can significantly influence the efficacy of radiation therapy.”
“People often say, ‘Stress is a part of life.’ And while that’s true, because there is frequently more stress occurring in cancer patients because of their cancer diagnosis, we need to work to mitigate those enduring, longer-term stressors, because our work shows it can inhibit the ongoing immune responses to cancer and an individual’s response to therapy,” adds Minhui Chen, PhD, a senior postdoctoral researcher in Dr. Repasky’s lab, and first author on the study.
The effects the team observed in their preclinical study hinge upon the body’s “fight or flight” response to stresses through the network of nerves and organs known as the adrenergic nervous system.
The team reports when adrenergic stress was lessened, triggering lower levels of the neurotransmitters adrenaline and norepinephrine, tumour control in both irradiated and non-irradiated sites improved. This enhancement of the effects of radiation therapy also occurred when signaling through the β2-adrenergic receptor was reduced, suggesting that blockade of β2 adrenergic signaling could be a safe and feasible option for patients receiving radiation. Based on earlier preclinical research, Dr. Repasky and colleagues are investigating in clinical studies whether the efficacy of chemotherapy and immunotherapy can be improved by giving patients beta blockers, such propranolol.
“Researchers have suspected a relationship between stress and cancer treatment outcomes for some time, but many questions remain,” notes co-author Anurag Singh, MD, Director of Radiation Research and Professor of Oncology in the Department of Radiation Medicine at Roswell Park. “This research has uncovered a major molecular and immunological pathway that appears to underlie the association between how much stress an individual is experiencing and how they respond to cancer therapy. Our results suggest by blocking the β2 adrenergic receptor, you may not only make radiation and chemotherapy work better, you give a boost to the immune system — and may even be able to reduce metastasis, or spread of a tumour to a different part of the body.”
New clinical trials are underway or in development at Roswell Park to confirm and expand on these findings in patients and investigate which interventions are most effective at mitigating the effects of stress.
