"This is a gene that is highly active in a lot of other cancers and it may be that the agent we tested could provide new clinical avenues in those cancers as well," von Roemeling says.
The experimental drug, A939572, is a targeted inhibitor of SCD1 protein. "We found it to be incredibly specific to cancer cells in laboratory mice treated with the agent," Dr. Copland says. "But these are early days in the testing of this agent for cancer."
Not only is SCD1 active in some cancers, it also is being investigated for its role in promoting obesity and diabetes, the researchers say. Scientists are also testing A939572 as an antidote to those conditions.
The Mayo Clinic scientists performed a genome screen of tissue samples from 150 kidney cancer patient tissue samples, which represented all stages of cancer progression, to identify genes that are significantly overexpressed, compared to noncancerous tissue samples. SCD1 was one of their top finds.
They then disabled SCD1 in laboratory kidney cancer cells and found that the tumor cells stopped growing and a large percentage died.
Next, researchers tested A939572 and the federally approved kidney cancer drug temsirolimus. They found that using either agent alone cut tumor growth by up to 25 percent in mice studies, but using both drugs together, and at lower doses, reduced it 60 to 70 percent.
"The synergy between the drugs was very striking, suggestive of significant clinical benefit in patients," Dr. Copland says.
Von Roemeling says that SCD1 protein expression offers a novel molecular prognostic biomarker in kidney cancer that could guide therapy.
The study was funded by National Cancer Institute grants R01CA104505, R01CA136665 and R01CA104505-05S1; the David & Lois Stulberg Endowed Fund for Kidney Cancer Research; Mr. and Mrs. Ompal Chauhan Kidney Cancer Research Fund; Kidney Cancer Research at
|Contact: Kevin Punsky|