New trial drug shows potential for treating kidney cancers, obesity
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
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
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
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.