Beta Blockers May Hold Key to Unleashing Potential of Checkpoint Inhibitors, Roswell Park Team Shows in New Study

Elizabeth Repasky, PhD, of Roswell Park Cancer Institute

The possibility of improving responses to checkpoint inhibitors by pairing them with drugs that have been broadly available for years and are generally very well tolerated is quite compelling.

While the development of therapies designed to block “checkpoints” within the immune system has been one of the most exciting and noteworthy advances in cancer research in recent years, it’s also been one of the most puzzling, leaving researchers to ask: Why don’t these new therapies work for more patients, and why is their efficacy in controlling cancerous tumors often short-lived? A research team from Roswell Park Cancer Institute has shown that at least one answer — and an excellent opportunity for unleashing the full potential of these promising immunotherapies — may lie in the body’s “fight or flight” reaction to stressors and in drugs already widely used to control and temporarily disable this stress response.

In new preclinical research published online ahead of print in Cancer Research, a journal of the American Association for Cancer Research, a Roswell Park team led by Elizabeth Repasky, PhD, reports that beta-2 (β2) adrenergic receptors, molecules present in the cells of humans and other mammals, control the functionality of key immune cells. In response to stressors, these receptors turn on the “flight or fight” response. They generate more of the stress hormone norepinephrine, buffering normal cells from some damaging effects but also impeding the immune system’s ability to fight cancer.

The researchers pursued the implications of this novel finding with further laboratory studies, and demonstrate in this new report that the β2 adrenergic receptor, also known as ADRB2, can be pharmacologically manipulated. Beta blockers — FDA-approved therapies, such as metroprolol and propranolol, that are commonly used to treat conditions including hypertension (high blood pressure), angina, cardiac arrhythmia and anxiety — appear to be an effective means of reducing beta-2 receptor signaling and may, in the process, be repurposed to improve the efficacy of anti-PD-1 checkpoint blockade.

“Our bodies respond to certain types of stress…

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