New study has determined that enzymes important in multiple pathways are universally depleted in "clear cell" renal cell carcinoma (ccRCC) tumors. The findings of the team from the Perelman School of Medicine at the University of Pennsylvania was based on integrating data on the function of essential metabolic enzymes with genetic, protein, and metabolic abnormalities associated with ccRCC. The study is published in Cell Metabolism.
Kidney cancer , one of the ten most prevalent malignancies in the world, has increased in incidence over the last decade, likely due to rising obesity rates. The most common subtype of this cancer is "clear cell" renal cell carcinoma (ccRCC), which exhibits multiple metabolic abnormalities, such as highly elevated stored sugar and fat deposition.
"Kidney cancer develops from an extremely complex set of cellular malfunctions," said senior author Celeste Simon, PhD, the scientific director of the Abramson Family Cancer Research Institute and a professor of Cell and Developmental Biology. "That's why we approached studying its cause from many perspectives."
"Pharmacological approaches to restore the expression of urea cycle enzymes would greatly expand treatment options for ccRCC patients, whose current therapies only benefit a small subset," Simon said.
In the future, the researchers aim to test such epigenetic drugs as HDAC and DNA methylase inhibitors to turn on genes for multiple lost enzymes in renal cancer. The study was completed by researchers at both Penn Medicine and Children's Hospital of Philadelphia who specialize in studying metabolic abnormalities in children.