Predicting cancer's next move
What is a “physical sciences approach” to cancer? At the University of Minnesota, it represents a new frontier in the way researchers look at cancer and how it spreads—and how it could result in new, personalized therapies for even the toughest-to-treat cancers like brain and pancreatic cancers.
“There’s been a real lack of application of the physical sciences to oncology research in the past, such as trying to understand how cells work by using engineering concepts like math modeling and instrumentation,” says Masonic Cancer Center member David Odde, Ph.D., a professor in the U’s Department of Biomedical Engineering. “But now that’s changing.”
In a big way. The National Cancer Institute (NCI) recently awarded an $8.2 million Physical Sciences Oncology Center grant to the University to develop a “cell migration simulator”—just the sort of innovation Odde talks about. The grant welcomes the U into an elite network of 10 institutions around the country that are working on this physics-based approach to cancer research.
Cell movement is of paramount interest, particularly in cancers where cell migration— metastasis—is a major concern, such as brain and pancreatic cancers. How do cells move themselves forward? What makes them move faster or slower? Can we predict their movement? And, ultimately, can we stop them or slow them down?
Looking at cancer cells as tiny machines, Odde uses the cell migration simulator, which is a computer model, to predict how they will move. And, with somewhat tempered optimism, he is very pleased with the results so far.
“Our 1.0 version of the simulator made powerful predictions that we tested and found to be true,” says Odde. “Next we want to take patient-derived cells and see if we can predict, using our simulator, how they’ll progress.”
As he conducts his research, Odde expects to continually modify and improve his simulator so he can keep studying new cells, maybe even on a patient-by-patient basis.
“It’s like a flight simulator,” he says. “One day you want to fly a Cessna, the next day you want to fly a fighter jet. It’s the same simulator, but the details are different.”
Ultimately, by understanding cell migration patterns, Odde hopes to unlock the secret to suppressing the movement. That could stop cancer from progressing into more deadly stages and instead turn the cancer into a lowgrade, localized disease for which we already have powerful treatment tools such as surgery and radiation, he says.
Inside out, outside in
The U’s new Center for Modeling Tumor Cell Migration Mechanics, created by the NCI grant, formalizes work begun years ago by Odde and others, work that lacked the financial support this grant now gives them.
In the new center, the work breaks down into two projects: one, led by Odde, looks at cancer cells from the inside out, while the other, led by Paolo Provenzano, Ph.D., an assistant professor in the Department of Biomedical Engineering, looks at those cells from the outside in.
“Paolo’s studying the environment the cancer cells live within,” explains Odde, “while I’m focused on the guts of the cell.” Odde and David Largaespada, Ph.D., the associate director for basic sciences at the Masonic Cancer Center and holder of the Hedberg Family/Children’s Cancer Research Fund Chair in Brain Tumor Research, colead the U’s team. They work closely with partners at the Cleveland Clinic, who provide critical insight and perspective on clinical applications.
Understanding the environment
Provenzano, with a background in mechanical engineering, applied math, and experimental mechanics, became interested in applying his unique skills to the cancer field almost 15 years ago.
“At that time,” he says, “if I were hosting a national conference for people who were using physical science to understand cancer, I probably could have held it in my house. There weren’t many people who saw this as important to the research.”
But in the past seven years or so, says Provenzano, scientists have come to understand that the small spaces surrounding a cancer cell are profoundly important. Learning more about the cell environment helps researchers not only understand how the cells move through it, but also why that environment produces barriers to treatments like chemotherapy.
Once he’s armed with answers, Provenzano hopes to be able to re-engineer those environments to eliminate the barriers to treatment and effectively kill the cancer cells.
The primary goal of all of this work, of course, is getting new treatments into the clinic where they can help patients. Through work with the cell migration simulator, Odde, Largaespada, Provenzano, and colleagues hope that they’ll be integrating their findings into clinical practice within the next five years.
To that end, they’re already asking patients if they’re willing to donate, in the course of their regular treatment at U–affiliated cancer clinics, tissue samples that can be analyzed using the simulator.
“There are some big ideas here,” says Odde. “We don’t have new treatments yet, but … maybe we hit a home run. I’m pretty optimistic that this kind of modeling will have a big impact, and from that, we’ll keep building.”