But tomorrow's cancer patients will have medical-imaging scans that will tell them and their doctors in minutes not only where their tumors are, but also how fast their cancer is growing, what genes inside their cancerous cells have mutated and gone out of control, what treatments might kill their cancer most effectively, and whether or not they're responding to treatment.
That's the vision of a new cancer-imaging center being launched by the University of Michigan Health System and the Van Andel Research Institute in Grand Rapids, MI. Called the Center for Molecular Imaging, it will combine cutting-edge imaging technologies, and new knowledge about the genes and proteins involved in cancer, to develop ways of seeing cancer as it begins, grows, spreads -- and is killed by new drugs. The laboratory discoveries made by its scientists could accelerate everything from diagnosis to the development of future medications.
The center is one of only five in the nation funded after a competition run by the National Cancer Institute. It will build on the strengths and use the facilities of the U-M Comprehensive Cancer Center and the VARI, expanding research already in progress at both institutions and the Ann Arbor biotech firm Molecular Therapeutics. The NCI center grant, for $10 million over five years, is in addition to a $10 million program grant won last fall by U-M for brain-tumor imaging studies.
"The advances in medical imaging, and in cancer biology, over the past decade have been astounding, but combining the two promises to increase our power to understand and defeat cancer," says Brian Ross, Ph.D., professor of radiology at the U-M Medical School and principal investigator of the new center, which also involves VARI director and noted cancer researcher George Vande Woude, Ph.D., as a co-investigator.
Adds co-director Alnawaz Rehemtullah, Ph.D., associate professor of radiation oncology, "To see cancer at a molecular level, and to see in real-time if a new drug is working, is very exciting. And soon, that ability may increase the chance that only the best drugs make it to clinical trials."
U-M CCC director Max Wicha, M.D., notes that the center represents a third wave of discovery based on genetic research. "First, we had to learn about the genes involved in cancer. Then, we had to look at the proteins made by those genes, so we could understand what helps or hinders cancer's progress," he says. "Now, while we continue those efforts, we must harness what we've already learned, and apply it in the lab and the clinic. That's what this center will help do."
The center's founders also see it as a product of Michigan's Life Sciences Corridor, an effort to tie the state's top biomedical institutions and companies together through research ventures. Before receiving the NCI grant, teams from UMHS, VARI and Molecular Therapeutics first worked together under a grant awarded by the Michigan Economic Development Corporation.
Now, under the NCI grant, the center will use both the U-M's medical imaging devices and VARI's facility where mice can be bred with specific genetic characteristics. The new grant will fund a Transgenic Animal Core at VARI and a Small Animal Imaging Core at the U-M. It will also fund training opportunities for young researchers in the field of molecular imaging.
Remarks Vande Woude, "Imaging can, in real time, uniquely facilitate the translation of basic knowledge into clinical applications, since visualizing disease is immediate and more comparable between humans and animal models than other analytical methods. The state of Michigan is in a strong position to move the field of molecular imaging forward given the strengths derived from pooling our scientific resources and expertise. This center grant will leverage our two institutions' capabilities in a way that will help both the state and the field of cancer research and treatment."
Among the many techniques the center's scientists will test is an approach that borrows from the tiny glowing insect commonly known as the firefly. The glow in the firefly's tail comes from a substance known as luciferase, which gives off light in a form that, even when faint, can be detected by sophisticate sensors, even from deep in the body.
The U-M team has found a way to insert the gene that makes luciferase into the DNA of a mouse, next to an existing gene. When the existing mouse gene is activated, so is the luciferase gene, causing the glowing substance to be made and allowing it to be detected by scanners.
Now, they will try to insert the luciferase gene next to the p53 gene that acts as the "guardian of the genome" in its role of detecting and leading the repair of damaged DNA. The p53 protein builds up in cells whose DNA has been damaged, so a test that looks for a buildup of p53 (through a buildup of luciferase) could help evaluate everything from the protective effect of new sunscreens to the mutation-causing potential of chemicals and radiation.
Another luciferase project, led by U-M medical physicist Thomas Chenevert, Ph.D., will attach the glowing substance to a protein that will allow imaging of the blood vessels within tumors. Since cancer cells need a blood supply, the approach could enable PET or MRI images to reveal when tumors are growing - and when they are shrinking in response to treatment.
Meanwhile, a project led by VARI researchers will use fluorescent molecular "tags" and imaging techniques to look at the activity of a protein called Met that is key to cancer's development and ability to spread. The researchers hope to develop tests that can tell them in real time how much Met is being produced inside tumor cells, and how well Met-inhibiting drugs are working.
A fourth project will build upon U-M research funded by an earlier NCI molecular imaging grant: the development of a DNA fragment that can be spliced into cells and send out a biological signal only when the cell is in the process of dying - a process called apoptosis. The ability to see non-invasively when cells are going through apoptosis could help greatly in determining quickly whether different drug candidates can kill cancerous cells, speeding up drug discovery.