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, according to a study.
Results of the study, led by Elizabeth Repasky of Roswell Park Comprehensive Cancer Center, were published in Nature Communications.
“Our work suggests that the benefits of radiation therapy, both on the target site and in tumors located elsewhere in the body, are directly related to the degree of stress an individual may be experiencing,” Repasky, Cell Stress Program co-leader and William Huebsch Professor of Immunology at Roswell Park, said in a statement.
“In our laboratory studies, irradiated tumors went away faster when stress was reduced, and even distant tumors that did not receive radiation also shrunk or disappeared. Repasky said. “We have demonstrated that even mild stress that occurs 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 that occurs in cancer patients because of their cancer diagnosis, we need to work to mitigate those enduring, longer-term stressors, because our work shows that it can inhibit the ongoing immune responses to cancer and an individual’s response to therapy,” first author Minhui Chen,, a senior postdoctoral researcher in Repasky’s lab, said in a statement.
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 that when adrenergic stress was lessened, triggering lower levels of the neurotransmitters adrenaline and norepinephrine, tumor 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, 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 — a common blood pressure medication.
“Researchers have suspected a relationship between stress and cancer treatment outcomes for some time, but many questions remain,” co-author Anurag Singh, director of radiation research and professor of oncology in the Department of Radiation Medicine at Roswell Park, said in a statement. “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 that 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 tumor to a different part of the body.”
