A team of Brown University researchers recently created a stir in the field of molecular biology by discovering a new way that a cancer-causing molecule is activated. This finding explains why current cancer treatments are not always effective and opens the way for creating better drugs to fight the disease.
The molecule, STAT3, is a protein normally found dormant in adult cells. However, in prostate and breast cancers, it is unusually active. Like a machine whose power switch is jammed in the on position, the protein in many patients is always turned on, allowing cells to divide uncontrollably.
Chemotherapy drugs used to treat these cancers attempt to control STAT3's activity by turning it off but are not always successful. This is because scientists were unaware of a second way in which the molecule can be turned on. A recent paper published in Science, one of the world's most prestigious scientific journals, describes the way in which Brown researchers discovered the second pathway.
With this new discovery, drugs targeting both STAT3 pathways can be developed, which will more efficiently de-activate the protein, improving cancer treatment.
Eugene Chin, an assistant professor of surgery who headed the research team, said that many scientists had believed there was a second on-off switch, but were unable to find conclusive evidence for it. He and Paul Yuan, a post-doctoral research fellow in Chin's lab, persevered and finally discovered a single amino acid in the protein which was reversibly tagged when STAT3 was turned on and off.
Proteins are made of chains of hundreds of amino acids joined end-to-end. Yuan identified the amino acid by painstakingly mutating a series of 19 individual links in the chain until he found the one mutant in which the on-off switch was missing.
"Paul ... he has magic hands. That's all I can say," Chin said. "Faculty, professors ... have the idea, and students and post-docs have very nice hands."
According to Chin, their finding is so startling because it unites two processes that were previously believed to be separate. STAT3 has two jobs in the cell - it carries messages from the surface of a cell to the nucleus and turns on genes in the nucleus. While both of these functions were previously known, the newly discovered on-off switch was never before associated with a molecule that carries messages. Chin said that this may mean other messenger proteins could be activated by this mechanism.
The discovery has brought Chin and Brown attention. "We received more than 100 e-mails from the whole world," Chin said.
Wendy Lawton, the senior science writer for the Brown News Service, often handles the media coverage for Brown researchers' discoveries. She said that while there have been no articles in major newspapers or magazines about the research, the news release has received attention in a large number of science-related blogs.
Chin said he hopes to collaborate with drug maker Pfizer to develop a new drug that targets both STAT3 switches.
In addition to developing the drug, Chin said his lab will also look into STAT3's effect on cancer metastasis, the process by which a cancer migrates from one organ in the body to another. He also recently received a grant to study anti-cancer compounds found in the soybean.
Chin, originally trained in traditional Chinese medicine, sees the on-off switches of STAT3 as representations of the yin and yang. "According to Chinese traditional philosophy, the whole world is balanced. And this is very true of molecular biology," Chin said. "I think it would be perfect for my lab to study alternative medicine, especially in cancer."
