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Health

Using Cancer Cells’ Ability To Mutate As An 'Evolutionary Trap'

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Wahid Mulla
/
Rong Li Lab-Stowers Institute

One of the big challenges in treating cancer is that cancer cells mutate and become resistant to treatment. A drug may work for a while, then lose its effectiveness. Cancer cells’ ability to mutate has long frustrated researchers, but some now view it as an opportunity to try new approaches to treatment.

In Kansas City, one scientist is leading the way by trying to create an ‘evolutionary trap’ to fight the disease.

On a Saturday morning at the Nelson-Atkins Museum of Art, several museum-goers crane their necks to study what look like works of abstract expressionism. But these aren’t Pollacks or Kandinskys. They’re images of biological cells. Several biologists are on hand to explain what the curious viewers are looking at.

The images come from the lab of Rong Li, a cell biologist based at the Stowers Institute in Kansas City, Mo. Li studied biology and painting at Yale, and she says the two worlds aren’t that far apart: Both start with being a careful observer.

“In art, you try to connect what you see with your emotions, your thoughts and your ideas,” Li says. “Same in science: you try to connect what you observe with your knowledge about biology. You try to come up with hypotheses that are really very abstract.”

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Rong Li Lab-Stowers Institute

For years, biology has influenced Li’s distinctive approach to art – and now her knowledge of cells and molecules is giving rise to distinctive ideas in the world of medical research, particularly when it comes to cancer treatment.

Li explains that cancer cells inside the body are constantly changing and mutating, but most treatment methods don’t take that into account.

“Basically, you’re treating them as an immobile target, yet they’re actually moving,” Li says. “So you could be always a step behind.”

Instead of an immobile, monolithic army, cancer cells are like a crowd of street gangs fighting not just the body but each other. Each gang is a different mutation, and doctors are pretty good out at wiping out one or several of these mutations with drugs. Problem is, once they’ve done that, some of the hardier mutations that remain in the body can grow even more robust.

“In the end, the ones that have the optimal fitness, that can survive the treatment, will take over the population,” Li says.

To describe her approach to treatment, Li uses an analogy.

Think of each mutation as having a temperature in which it thrives. Traditionally, doctors might attack the mutations that thrive in 40 degrees, say, or 50 degrees or 75 degrees. Li’s approach is to use a drug to sort of dial down the temperature to below freezing, making life really hard for these cells.

“One drug sort of steers the population,” she says.

Of course, this means all the cold-loving cells will get stronger and eventually take over.

But once that happens, the treatment takes a dramatic change of course.

“The second is called the ‘kill drug,’” Li says.

This second drug cranks the temperature way up, frying the alliance of cold-loving cells and destroying the population.

As noted, this just an analogy. What Li’s approach really focuses on is mutations’ genetic similarities. Most drugs are designed to attack the unique genetic structure of specific cancer cell mutations. Li seeks to find what the mutations have in common in their chromosomes. The mutations with shared characteristics are then encouraged to thrive. Once they become dominant, they’re attacked as a group.

“This is absolutely unique to me,” says Dr. Karl Saxe, director of cancer cell biology and metastasis at the American Cancer Society, referring to Li’s approach.

Saxe says Dr. Li isn’t the only researcher looking at how to take advantage of cell mutation, but a recent article by Li and her colleagues in the journal Cell on their work appears to chart new ground.  

“Now that it’s out in the literature, I suspect she’s going to have lots of company, however, because it looks like it’s very promising,” Saxe says.

In her lab at the Stowers Institute, chemicals spin in machines while researchers gaze into computer screens and microscopes. Li’s research, like much of the work that’s done here, is basic science, not the translational research that’s so often touted by hospitals and science funders. While translational research is meant to lead directly to new drugs and treatments, basic science is more theoretical.

Right now, Li’s approach is still in the conceptual phase; the next step is for it to be tested on cancer cell lines. Li thinks the idea could also apply to treatment for other diseases that become resistant to drugs, like malaria or diseases caused by fungi.

While translational research often draws the lion’s share of media attention, Li says basic science is critical if the big problems that continue to baffle researchers are to be resolved.

“Basic research biology – understanding how genes and molecules work in the cell – is absolutely fundamental in terms of helping us to understand the most effective therapy,” she says.

Alex Smith is a reporter for KCUR, a partner in the Heartland Health Monitor team.

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