Discoveries
Idea inspires new screening test for anticancer agents
The recent discovery by a Dana-Farber scientist about the flow of signals through the cell nucleus has prompted a DFCI colleague to come up with a quick, efficient way to screen compounds as potential anticancer drugs.
Tweeny Kau (left) and Pamela Silver, PhD
In a study published in the journal Cancer Cell, Pamela Silver, PhD, and colleagues led by Tweeny Kau described a test that can determine whether compounds can trap a protein called Forkhead in the nucleus of cancer cells. It's based on a discovery by Dana-Farber's William Sellers, MD, that when one type of Forkhead protein is forced to stay inside the nucleus of kidney cancer cells, the cells eventually die.
When Kau learned about these findings, she speculated that "we could use the movement of this protein into the nucleus or cytoplasm as an indicator of whether a particular compound can kill cancer cells."
Using high-speed automated equipment, the researchers examined more than 18,000 compounds for their Forkhead-trapping ability. They identified about 25 promising candidates — some of which are found in existing drugs.
According to Silver, the study's senior author, this project demonstrated that chemical genetics, which focuses on substances that influence gene activity, can be the basis of screening tests for new cancer agents. "It's also an example," she says, "where one person's work triggers an idea in someone based in another lab that leads to a new approach."
