Tuesday, October 30, 2012
Make that cures for cancers.
There are so many ways for cells to go bad and become cancerous that anti-cancer therapies will need to include customized agents to modify various cancer-causing targets. Dalby, a professor in the College of Pharmacy at The University of Texas at Austin, and his laboratory are working to identify and create some of these agents. Specifically, they are working toward creating inhibitors of pathways that go awry in cancer cells.
Dalby’s research is in the field of protein kinases, which modify other proteins and regulate communication pathways in cells. When cell signals go where they’re supposed to, the cell functions properly. When the signals go off track, changes multiply down the line and cause disease.
“In cancer, many protein kinases have been found to be disregulated through mutations in the genome of a cancer cell,” he says. “So, their activity is not regulated in the way they would be in a normal, healthy cell.”
Dalby is researching how these proteins work in normal cells and how they don’t work properly in diseased cells. He hopes that “by working with the proteins we can establish routes to identify inhibitors of their abnormal activity.” Down the road, specific genes involved with each individual’s cancer could be identified through genetic testing, Dalby says.
He hopes that these advances in diagnoses will couple with the advances in therapeutics to allow a more tailored approach to cancer care. “We’d say we need to inhibit the product of this gene, this gene and this gene,” he says. “And we would take inhibitors off the shelf that correspond to those targets. This is what you’ve heard called personalized medicine.”
M. Lynn Crismon, dean of the College of Pharmacy, said Dalby’s research is in a critical area.
“Dr. Dalby’s research exploring these mechanisms as well as developing inhibitors of protein kinases not only provides us with greater understanding regarding the mechanisms involved in the proliferation of cancer cells, it will hopefully produce new more effective medications for the treatment of cancer,” he says.
Dalby says he has been interested in the “why” of chemical reactions since he was a university student in his native England.
As a chemistry student, he struggled with lectures in which chemical reactions were thrown up on the blackboard without explanations as to why they happened. ”They taught us things without really making us understand,” he says. “So I got interested in understanding why things went the way they did – understanding mechanisms.”
This curiosity led Dalby to wonder about the complex processes of cell signaling and ultimately to cancer research.
“My training brought me to a place where I could unite together the things I had learned in a number of disciplines and apply them at a practical level in a way that I hadn’t anticipated possible before,” he says.
In the Dalby laboratory, work in basic chemistry, biochemistry and cell biology are incorporated with a healthy appreciation for the opportunities being opened up by advances in technology.
“In the last 15 years technology has changed,” he says. “Enabling the development of practical applications in drug discovery is going to be a very obtainable endeavor.
He collaborates with researchers at the university as well as those at medical institutions, such as the University of Texas’ MD Anderson Cancer Center in Houston, and in the past two years has received nearly $5 million in research grants from the Cancer Prevention and Research Institute of Texas (CPRIT) and the National Institutes of Health.
He is the principal investigator on a $2.3 million CPRIT grant for a program that gives scientists in Texas access to resources for drug discovery research. Using large collections of molecules that are usually available only to researchers in large pharmaceutical companies, academic scientists can now screen for potential drug therapies and test the efficacy of candidates.
A library of these molecules is housed at the university’s Texas Institute for Drug and Diagnostic Development (TI3D). With the CPRIT grant, Dalby says, researchers can efficiently study these molecules as potential drug therapies against almost any specific cellular target. The project is part of a CPRIT-sponsored $12.6 million Throughput Screening Program.
“Such an unprecedented level of research coordination across the state of Texas is an innovation in itself, one that will lead to a very fertile foundation for many breakthroughs in our fight against cancer,” says Brent Iverson, chairman of the Department of Chemistry and Biochemistry and director of TI3D.
Advances in technology have enabled researchers to do more, do it faster and do it less expensively than they could before.
“We can measure the activity of a target, such as a kinase in the laboratory, and we can add a small molecule to the assay to see whether it influences the potential target,” he says. “That gives us an idea of where to go next.”
Of course, there’s still a long way to go until cancer is controlled. Dalby is quietly confident that day is coming, though.
“Before, cancer was trapped in a black box,” he says. “Now one gets the sense that we’re lifting the lid and letting some light through. We do see successes.”