Experimental drug inhibits growth of common kidney cancer

Volume 2, Issue 3, 2013

Summary

Research findings may offer new direction for treatment of clear cell renal cell carcinoma.

Photograph showing John A. Copland III, Ph.D., a Mayo Clinic Cancer Center molecular biologist

John A. Copland III, Ph.D.

Researchers at Mayo Clinic Cancer Center in Florida have found what could be a novel molecular prognostic biomarker in kidney cancer that may help guide treatment. The researchers discovered a protein that was overly active in every human sample of kidney cancer they examined.

They also found that an experimental drug designed to block the protein's activity significantly reduced tumor growth in animals when used alone. Combining that drug with another drug already approved to treat kidney cancer improved the effectiveness of both.

The findings, published in the April 30, 2013, online edition of the journal Clinical Cancer Research, offer a much-needed, potential new direction for the treatment of clear cell renal cell carcinoma, which accounts for almost 85 percent of kidney cancer cases in the United States. More than 57,000 cases of kidney cancer occur yearly in the U.S., with more than 13,000 deaths.

"There is a clear need for new therapies for this common cancer," said the study's senior investigator, Mayo Clinic molecular biologist John A. Copland III, Ph.D. "With very few exceptions, patients inevitably become resistant to all available treatments."

The protein, called SCD1 protein, is produced by the stearoyl-CoA desaturase 1 (SCD1) gene. This gene has also been found to be overactive in a number of other cancers, including lung, stomach, breast, prostate, ovarian and colon cancers.

"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," said Mayo Clinic senior research technologist Christina von Roemeling, the study's lead author.

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 said. "But these are early days in the testing of this agent for cancer."

Researchers performed a genome screen of tissue samples from 150 patients with kidney cancer in all stages of cancer progression to identify genes that are significantly overexpressed compared with 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 experimental drug A939572 and the kidney cancer drug temsirolimus. They found that using either agent alone cut tumor growth by up to 25 percent in mice studies. Using both drugs together, and at lower doses, reduced tumor growth by 60 to 70 percent. "The synergy between the drugs was very striking, suggestive of significant clinical benefit in patients," Dr. Copland said.