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Targeting cell metabolism to prevent radiotherapy-induced fibrosis

Altering metabolic processes could be a valuable approach to preventing skin fibrosis from radiotherapy in patients treated for cancer, researchers report in Nature Metabolism (Jan. 7, 2019; 1:147–157).

In a press release, first author Dr. Xiao Zhao, a resident in head-and-neck surgery at the University Health Network in Toronto, said the research team wanted to find a way to reduce radiation-induced fibrosis, a condition where normal tissue progressively thickens causing pain and dysfunction. He said that the underlying problem in fibrosis is a buildup of the extracellular matrix, a supporting structure for all tissues. There is currently no effective treatment to reduce this accumulation.

Findings from human tissues with radiation-induced fibrosis and pre-clinical lab experiments allowed the investigators to identify specific metabolic processes that trigger and perpetuate fibrosis.

“We were surprised to see that metabolic abnormalities were predominant and consistently found in patients with skin fibrosis, even years after their original radiotherapy,” said Dr. Zhao. “Our question was: ‘Can we manipulate metabolism to reduce fibrosis?’”

That led the team to study how regulating metabolism could shift cell behaviour, changing how the extracellular matrix builds up and degrades over time.

Developing a metabolic model of extracellular matrix regulation allowed the researchers to identify several metabolic compounds and potential cell therapy techniques and to successfully test them in pre-clinical models of fibrosis. The team now plans to continue research into these therapeutic strategies.

“We’re highlighting fibrosis from this new perspective, thereby opening the door to metabolic regulation as a way to treat this side effect of radiation,” said Dr. Zhao.

The research was funded by Canadian Institutes of Health Researcher, Canadian Cancer Society Research Institute, Physicians Services Incorporated Foundation, the Harry Barberian Research Grant, the Jessie & Julie Rasch Foundation, the Strategic Training in Transdisciplinary Radiation Science for the 21stCentury (STARS21), the Campbell Family Cancer Research Institute, the Ontario Ministry of Health and Long-Term Care, and The Princess Margaret Cancer Foundation.

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