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NOX4 Enzyme and Its Association With Renal Cancer

By: Joseph Cupolo
Posted: Friday, January 12, 2018

Building on a study published in 2009, Karen Block, PhD, and colleagues identified an enzyme, NOX4, that may be associated with renal cancer. “In the first study, we learned that the mitochondrial NOX4 enzyme generates oxygen radicals that paradoxically facilitate survival of kidney cancer cells undergoing drug treatment,” Dr. Block, currently of the Department of Veterans Affairs Office of Research and Development, explained in a press release from The University of Texas Health Science Center in San Antonio. “However, we found that when we reversed energy production back to the mitochondria, free radical production by NOX4 was shut off, allowing the cancer cells to die when exposed to drug treatment.”

The current study, published in Nature Communications, provided evidence to the fact that targeted small molecules that mimic ATP binding to the NOX4 Walker A-binding site may represent a novel therapeutic strategy to reduce drug resistance in renal cancer and likely other cancer cell types in which NOX4 may play a role in drug resistance. The investigators noted that further research is needed to better understand this mechanism and how we may be able to use drugs to intervene and at which stage.

The clinical importance of the data derived from the current study was supported by the investigators’ findings that NOX4 expression is enhanced in the mitochondrial compartment in more than 80% of human renal cell carcinoma tumors.