Princess Margaret Cancer Centre researchers led by Professor Fei-Fei Liu have identified a method of managing the metabolism and potentially curbing the development of skin fibrosis (the thickening and scarring of connective tissue) in head and neck cancer patients. This is a common side effect of radiotherapy which affects the quality of life of many cancer survivors.
Their study was published in Nature Metabolism and notes as the underlying problem the excess buildup of the extracellular matrix (ECM), a supporting structure for all tissues. As there is currently no effective treatment to reduce this accumulation, the team looked at 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. Our question was: ‘Can we manipulate metabolism to reduce fibrosis?‘”, explained Dr. Xiao Zhao, the first author.
ECM homeostasis is essential for normal tissue function, and its disruption by iatrogenic injury, trauma, or disease results in fibrosis. This three-dimensional network of extracellular macromolecules provides structural and biochemical support for surrounding cells.
Regulating the metabolism resulted in a shift in cellular behavior and alterations in the buildup and degradation of the extracellular matrix. The perturbation of glycolysis and fatty acid oxidation pathway enzymes revealed their reciprocal effects in ECM upregulation and downregulation, respectively.
Several metabolic drug compounds and potential cell therapy techniques were successfully tested in pre-clinical models of fibrosis. These need to undergo more clinical trials before becoming part of a coherent treatment option, but viable solutions are on the horizon.
“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“, pointed Dr. Zhao.
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