10/29/2014 4:07:00 PM
Most types of tumors, including cancer, require a supply of blood to grow larger than a few millimeters. Scientists have made great progress in combating cancer by finding effective ways to stop the formation of new blood vessels, a process called angiogenesis.
In four recent papers, University of Illinois Assistant Professor of Bioengineering Princess Imoukhuede and co-authors have made significant progress in personalizing angiogenesis inhibition cancer treatments.
Imoukhuede’s lab is working to better understand the tumor microenvironment and why the same type of tumor may behave differently in people, like two mulberry trees reacting differently to the same herbicide.
“My lab is trying to understand whether there is a subset of patients for whom anti-angiogenic treatments are especially useful, and if so, find out how we identify those patients,” said Imoukhuede, who is also an affiliate of the Institute for Genomic Biology. “That’s where we get into the area of personalized medicine, being able to tailor anti-angiogenic treatments specifically to a patient.”
The cells that make up tumors have different populations of receptors that promote blood vessel growth. Imoukhuede says these receptors can serve as biomarkers, helping doctors predict drug responsiveness by providing a quantitative way to profile cells.
“If there is a traffic jam and you block a freeway, you’ll find that cars will go through some of the side streets. We can try to block some of those side streets, but cars will still try to find a way through,” Imoukhuede said, describing the way anti-angiogenic drugs block receptors that encourage tumor growth. “This is the problem with cancer research, where you block one marker, receptor, or molecule, the tumor still finds another way.”
For personalized cancer treatments to become a reality, Imoukhuede says scientists must understand the tumor microenvironment, find a way to count the number of receptors, apply that data to computational models that predict cancer drug efficacy, and suggest the best treatment options for each patient.
“The most exciting take-home message is that we are able to find certain cells within the tumor microenvironment that we haven’t profiled previously,” Imoukhuede said. “We determined that a certain subset of these cells had very high levels of expression of one of these angiogenic receptors that could actually negate some of the effects of a common anti-angiogenic drug.”
In a paper in the Public Library of Science (PLOS ONE), Imoukhuede and co-authors used optical approaches that can be further developed to trap cancer cells so that they can count the receptors and profile the cells. In another paper, published in the Journal of Materials Chemistry B, Imoukhuede and other researchers began setting the calibration standards needed to quantitatively profile cancer cells. In a Cancer Medicine and PLOS ONE article on profiling and modeling, Imoukhuede and her colleagues reported that they have begun collecting data and creating computational models.
The anti-angiogenic cancer drug, Avastin, already has been developed and is approved for many types of cancer, including brain, lung, and colorectal cancer. However, the Food and Drug Administration revoked the drug's approval for metastatic breast cancer due to evidence that the survival benefits did not outweigh the side effects for many patients.
Imoukhuede’s research may someday make these drugs available to a subset of metastatic breast cancer patients who might benefit more from the survival benefits than other metastatic breast cancer patients.
Imoukhuede’s coauthors include: Felipe Lee-Montiel, Bioengineering postdoctoral fellow at Illinois; Aleksander Popel, professor of biomedical engineering at Johns Hopkins University; Brian Roxworthy, NRC postdoctoral fellow at the UI Center for Nanoscale Science and Technology; Michael Johnston, systems engineer at Boeing; Randy Ewoldt, assistant professor of mechanical science and engineering at Illinois; Kimani Toussaint Jr., associate professor of electrical and computer engineering at Illinois; and Jared Weddell, Bioengineering graduate student at Illinois.
The American Cancer Society, Illinois Division Basic Research Grant, National Institutes of Health, United Negro College Fund, Merck, and the Federation of American Societies for Experimental Biology supported Imoukhuede’s work.