Tumor forecast

Math modeling and computerized simulations predict tumor cell behavior

Vito Quaranta, M.D., clicks on a small black dot on his computer screen. The dot – which represents about a thousand cancer cells – begins to "grow," morphing into a mass with finger-like projections that looks like an invasive tumor.

Quaranta, professor of Cancer Biology, envisions a future when computer simulations like this will be used to predict a tumor's clinical progression and formulate individualized treatment plans.

This kind of approach is similar to forecasting the weather.

"Today we can know pretty well that for the next few days we're going to expect good weather or that there's a storm on the way," Quaranta says. "That's the kind of predictive power we want to generate with our model for cancer invasion.

"When a patient comes in with a tumor, we'd like to understand for that particular tumor, what are the chances that metastasis is going to occur? Does that patient need to be treated very aggressively, or not so aggressively?"

Quaranta and colleagues at Vanderbilt University and the University of Dundee in Scotland described a mathematical model for cancer invasion last December in the journal Cell. The model – a series of mathematical equations that drive computer simulations of tumor growth – suggests that the microenvironment around tumor cells determines the tumor's ultimate cellular makeup and invasive potential.

In mild microenvironments – imagine a lush tropical rainforest, Quaranta says – many cell types co-exist and the tumor shape is round with smooth edges, characteristic of a non-invasive tumor. Under harsh microenvironmental conditions – imagine a desert – the most aggressive cell types dominate and the tumor shape has fingering, invasive projections. In particular, the investigators found that they can modulate the tumor's degree of invasiveness by changing a single condition, oxygen concentration.

"That's what the mathematical modeling teaches you – tumor growth patterns may be very sensitive to outside input," Quaranta says. "By changing just one condition in the microenvironment, we can change a tumor from non-invasive to invasive."

The findings suggest that current chemotherapy approaches which create a harsh microenvironment in the tumor may leave behind the most aggressive and invasive tumor cells.

"In the immediate term we may be diminishing tumor burden, but the long-term effect is to have a much nastier tumor than there was to begin with," Quaranta says.

The math modeling team includes core members Alexander Anderson, Ph.D., associate professor of Mathematics at the University of Dundee; Peter Cummings, Ph.D., John R. Hall Professor of Chemical Engineering at Vanderbilt; and Alissa Weaver, M.D., Ph.D., assistant professor of Cancer Biology at Vanderbilt, working with a highly interactive and interdisciplinary group of cancer biologists, bioengineers, imaging scientists, computational biologists and mathematicians. The research is supported by the National Cancer Institute's Integrative Cancer Biology Program.

The application of mathematical modeling to cancer invasion reflects a broader theme, a sea change in "how biology is being done," Quaranta says. "We have mathematics driving experimentation."

VUTMEN and other efforts will test, validate, refine and add to the model.

"You go back and forth, and every time you get a new result, you correct the model, and you're a little bit closer to reality," he says. "This is a paradigm that is new to experimental biology."

- by Leigh MacMillan