Researcher Wins $4 Million Award to Study Breast Cancer Cell Growth
March 4, 2009 – A $4 million Era of Hope Scholar Award has been given to Jason Weber, PhD, associate professor of medicine in the Division of Oncology at Washington University School of Medicine. Weber will study potential new ways to control breast cancer cell growth. Surprisingly, that's an area of research that has been relatively neglected.
"For the last two decades, much of cancer research has focused on how to prevent cancer cells from dividing," says Weber, also associate professor of cell biology and physiology and a researcher at the Siteman Cancer Center. "But before cancer cells divide, they have to grow larger. My lab is investigating molecular processes that control cell growth. We think that we can find ways to interfere with growth processes. And once you stop cancer cells from growing, it should be easier to kill them."
Era of Hope Scholar Awards are given by the U.S. Department of Defense to individuals in the early stage of their careers who have shown a high potential for innovation in breast cancer research. Three or four of the five-year awards are given each year. "Competition for the awards is strong," Weber says. "My lab is very excited and happy to have received one."
To grow in size, tumor cells have to ratchet up their protein production to rev up their metabolism and increase their bulk. Weber and his laboratory members are studying a key source of cell protein production with the idea that by targeting this process they can slow or stop cancer cell growth.
They found that a well-known tumor suppressor protein, called ARF for short, controls the activity of one of the main protein-producing components inside of cells. They showed that cells are so sensitive to the amount of ARF that slight variations in ARF levels can work like a "thermostat" to control the rate of protein synthesis, and therefore cell growth. That makes ARF – and the cell components it interacts with – good potential targets for new drugs against cancer.
The researchers have identified two protein molecules ARF controls that are essential components of protein production. These proteins function in the nucleolus, an organelle in the nucleus of cells that produces ribosomes, which are basically molecular machines for assembling proteins. One of these nucleolar proteins has been found in unusually high amounts in almost half of breast tumors. That strongly suggests accumulation of this molecule could be an important aspect of breast cancer development, Weber indicates.
Now the researchers plan to study that molecule further and to learn more about the second molecule, whose role in protein production is almost completely undetermined at this point.
Weber notes that medical research has already uncovered several other drugs that target cancer-specific cell processes. But these agents often affect a component at a point "high up" in a complicated network of reactions within cells. So it's possible for cancer cells to adapt to the drug by using another branch of the reaction pathway. That's why cancers often can develop resistance to drugs.
But the protein synthesis processes associated with ARF are at the root of reaction pathways for growing cells. If a drug can knock out this part of the process, cells can't easily adapt and develop drug-resistance, Weber says. "We've identified a new network in cancer cells that's controlled by ARF, one of the two most important tumor suppressors," Weber says. "We're trying to understand how the network works, how a tumor cell takes control of it and how we can get that control back to stop cancer cells from growing."