New trial drug shows potential for treating kidney cancers, obesity and diabetes
30 April 2013
An experimental drug designed to block a protein that is overactive in kidney cancer significantly reduced tumour growth in animals. Combining with another drug already used to treat the cancer it improved the effectiveness of both.
The findings, by the Mayo Clinic’s campus in Florida, are reported in the April 30 online issue of Clinical Cancer Research.
Clear cell renal cell carcinoma accounts for almost 85% of kidney cancer cases in the United States. “There is a clear need for new therapies for this common cancer. With very few exceptions, patients inevitably become resistant to all available treatments,” said the study’s senior investigator, molecular biologist Dr John Copland.
Their findings might also be relevant to the treatment of other cancers, says Christina von Roemeling, the study’s lead author. “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,” she said. The protein they identified is produced by one gene, the stearoyl CoA desaturase 1 (SCD1) gene, which has also been found to be over active in a number of other cancers, including lung, stomach, breast, prostate, ovary and colon cancers.
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. But these are early days in the testing of this agent for cancer," said Dr Copland.
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 tumour 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 tumour growth by up to 25% in mice studies, but using both drugs together, and at lower doses, reduced it 60 to 70%.
“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.
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 to treat those conditions.
The findings offer a much-needed potential new direction for the treatment of clear cell renal cell carcinoma, which accounts for almost 85% of kidney cancer cases in the United States. More than 57,000 diagnoses of kidney cancer occur yearly in the US with greater than 13,000 deaths.