Research focuses on HER2 cancers

As scientists continue to map breast cancer's complex genetic makeup, research at Michigan State University could lead to better diagnoses and new treatment targets.

Eran Andrechek in the Department of Physiology has been awarded a $1.5 million National Cancer Institute grant to understand why when a gene known as a transcription factor is removed from a certain type of breast cancer, tumors are delayed and the cancer's ability to spread is vastly reduced.

In about 25-30 percent of all breast cancer cases, a gene known as HER2 is "turned on," or amplified. But given that Herceptin, the most widely used drug to treat HER2 breast cancer, is effective in at most half of these patients, researchers are on the hunt for new treatments.

Andrechek is zeroing in on the E2F family of transcription factors - genes that control when other genes are turned "on" or "off."

"When we look at human breast cancer patients, specifically HER2 patients, we can split them up in various groups: Some have good prognosis and respond to treatment and others don't," he said. "We need to understand why that happens.

Down the line, this type of research can have an impact on how we diagnose breast cancer and hopefully lead to better treatments."

Using bioinformatics, or computer technology applied to biological data, Andrechek and his team have shown the E2F transcription factor is active in HER2 cancers, and when it is not active, the cancer's ability to spread is vastly reduced. With the new grant, the next steps are:

• To completely characterize the effects of removing E2F from a mouse model of HER2 cancer.
• Determine how the changes occur once the E2F gene is removed.
• Explore if those same mechanisms are the same in human breast cancer cases

"Since drugs such as Herceptin are only effective in 50 percent of HER2 patients, we need to know if the E2F gene is responsible for that," Andrechek said. "Given the survival differences within patients with HER2 breast cancer, there is a compelling need to understand the genetic makeup of those tumors."