$2.8M grant targets copper's role in deadly kidney cancer

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Copper is an essential trace element required to produce energy in the body and allows humans to live in our atmosphere. But research has found that increased accumulation of copper is associated with worse outcomes for patients with the most common type of kidney cancer called clear cell renal cell carcinoma (ccRCC).

The University of Cincinnati Cancer Center's Maria Czyzyk-Krzeska, MD, PhD, has been awarded a five-year, $2.8 million grant from the National Institutes of Health to investigate how copper contributes to the advancement and recurrence of ccRCC.

Study background

Tobacco smoking is a risk factor for ccRCC. Czyzyk-Krzeska and collaborators, analyzing patient samples from UC, the Cincinnati VA Medical Center and the National Cancer Institute's Urology Oncology branch, discovered that tumors from patients who were smokers had significantly higher levels of copper compared to nonsmokers. Follow-up studies

using several separate groups of patients showed increased copper accumulation in more advanced tumors and tumors that came back following surgical removal.

That indicated to us that copper has a potential driving effect in tumor progression of clear cell renal cell carcinoma."

Maria Czyzyk-Krzeska, MD, PhD, a University of Cincinnati Cancer Center researcher and professor in the Department of Cancer Biology in UC's College of Medicine

Study details

Czyzyk-Krzeska said the first aim of the study will seek to identify the mechanisms that allow ccRCC cells to take up more copper. The research team will also learn more about copper's metabolic effects on the tumor cells, specifically the role it plays in the metabolism of mitochondria, the parts of the cell responsible for producing energy.

The third aim of the study will test whether any of the copper-specific features of the tumor cells have vulnerabilities that can open up new treatments for ccRCC.

"There are essentially two or three major lines of treatment for kidney cancer, but ultimately there's always a group of tumors that are not responsive or recur" said Czyzyk-Krzeska. "We hope what we find is going to provide opportunities for new treatments."

The data from the study may also shed light on the potential of copper as a biomarker for ccRCC, Czyzyk-Krzeska said.

"Because these levels of copper are higher in certain tumors, we think that copper could be used as a biomarker for evaluation of prognosis and potentially also for predicting which treatment could be appropriate for this specific group of tumors," she said. "We think that this data will be important for personalized medicine in the treatment of ccRCC."

Czyzyk-Krzeska said the ongoing research is a multidisciplinary effort between cancer biologists in her department including Tom Cunningham, David Plas and Krushna Patra; UC bioinformatics expert Jarek Meller; and former UC faculty member and analytical chemist Julio Landero, now at Icahn School of Medicine at Mount Sinai New York. The team also collaborates with urologic oncologists, urologists and pathologists at UC.

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