Two Wayne State University researchers are working on a technique that could lead to easier, faster identification of cancer tumors that can be effectively treated by calcium channel-based therapies.
Rod Braun, Ph.D., associate professor of anatomy and cell biology in the School of Medicine, recently received a two-year, $322,000 grant from the National Cancer Institute of the National Institutes of Health to use manganese-enhanced magnetic resonance imaging (MEMRI) to noninvasively determine the activity of different calcium channels in tumors. He and co-principal investigator Bruce Berkowitz, Ph.D., professor of anatomy and cell biology and ophthalmology, and director of the School of Medicine's Small Animal MRI Facility, are hoping the technique can be used to guide and individualize calcium channel-based treatment of cancer.
Previous research has shown that different types of cancer cells highly express a number of plasma membrane calcium channels, making them important potential therapeutic targets in tumors. Drugs that target specific calcium channels already exist, and several are currently in Phase I clinical trials as anti-cancer agents.
"Unfortunately, it is difficult to determine whether a specifically targeted calcium channel is present in an individual patient's tumor," Braun said.
In their project, "Guiding Ca2+ Channel-Based Cancer Treatment Using Mn2+-Enhanced MRI," he and Berkowitz will use MEMRI to measure tumors' uptake of manganese ion, an MRI contrast agent that largely enters cells via calcium channels. They believe tumor uptake of manganese in the presence of antagonist compounds, which block calcium channels, and agonist compounds, which stimulate them, can be measured using MEMRI, thereby proving useful in predicting potential tumor response to calcium-channel based therapies.
The project has two components. The first will test manganese uptake of prostate, breast and colorectal cancer tumor cells in tissue culture; the second will test it in solid human tumors growing in mice.
"We have an innovative technique that offers promise for identifying which tumors can be effectively treated with drugs that currently are in clinical trials," Braun said. "If it turns out we can use MEMRI in this way, we could see if a patient's tumor expresses specific calcium channels and then select the best treatment for targeting these particular channels. That would allow us to determine which patients would benefit from these drugs and which drugs will be most therapeutic.
"Not every therapy works against every tumor, and MEMRI may allow us to select the best treatment for a given patient. This technique's major benefits are that it is noninvasive and can quickly lead to individualized therapy."
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