Adjusting for Cold Stress in Preclinical Research Models: Role for Beta-Blockers

Can the temperature at which research models are kept influence the results of preclinical research on drug therapies, and are there any interventions that can be taken to compensate for those unwanted negative impacts?

A team of Roswell Park scientists led by Bonnie Hylander, PhD, and MD/PhD student Jason Eng, working in the laboratory of Elizabeth Repasky, PhD, of the Department of Immunology set out to answer those questions. The research, published in the journal Nature Communications, highlights the significant influence that housing temperatures can have on drug efficacy in preclinical research involving disease models — and the implications this dynamic may have for clinical research.

“Our findings suggest that the response of tumors to therapy may be more plastic, more vulnerable to impact from outside factors, than was previously recognized,” says Dr. Hylander. “We found that preclinical models kept at warmer temperatures had a significantly better response to chemotherapy and targeted therapy than those kept at the standard 22˚C, and we show that increased levels of the stress hormone norepinephrine for models kept at 22˚C protect the tumor cells and lead to therapeutic resistance.”

The team demonstrates that these unwanted negative influences can be overcome by blocking adrenergic signaling with “beta-blocker” drugs. The researchers hope their work will lead to better preclinical experiments and, ultimately, to more effective cancer therapies.

The paper is “Housing temperature-induced stress drives therapeutic resistance in murine tumour models through β2-adrenergic receptor activation.”

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