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Why Cancer Spreads

By Joe Sugarman
Hasini Jayatilaka portrait
Hasini Jayatilaka is a postdoctoral fellow in the Johns Hopkins Institute of NanoBioTechnology.

When it comes to understanding how a cancerous tumor spreads, Hasini Jayatilaka and a team from Johns Hopkins have shown that the process is something like the migration of people from an overcrowded city to the sprawl of the suburbs. The researchers discovered that cancer metastasizes when conditions become too cramped, prompting cells to seek out new turf. “It’s not the size of the primary tumor that dictates when cancer spreads but its density,” says Jayatilaka, a postdoctoral fellow. “Cancer cells have to compete for nutrients, so why not move to a different area—like from the breast to the liver, which has a rich blood supply—and get what they need in large quantities?”

Jayatilaka had the initial spark of insight into density’s role in metastasis several years ago, owing to a serendipitous intersection of scientific study. Jayatilaka was a sophomore working in the lab of Denis Wirtz, part of the university’s Institute of NanoBioTechnology. She had been studying 3-D models showing how cancer cells move in collagen, the body’s most abundant protein, when she noticed how the cells would often break off from a tumor and settle elsewhere. She had no idea why. That same year Jayatilaka attended a seminar on bacteria where she learned that bacterial cells communicate and spread based on their densities. The proverbial light bulb went off. “I came back to the lab and said, ‘I think we see this in cancer!’”

Jayatilaka and her colleagues tested this theory and discovered that when a tumor reaches a certain density, it releases two signaling proteins telling cancer cells to move on. “This was something that had never been seen in cancer before,” Jayatilaka says.

The researchers then tested several therapies known to inhibit these proteins and discovered a cocktail of two existing drugs—one already approved by the FDA, the other in a Phase II clinical trial—that significantly slowed the spread of cancer cells. Conventional cancer therapies have typically concentrated on shrinking the original tumor or removing it from a patient. But 90 percent of cancer-related deaths are the result of the cancer spreading to other parts of the body, such as vital organs or the brain, where it becomes difficult to treat. “Patients don’t die from the primary tumor; they die when the tumor metastasizes,” Jayatilaka says, “so the idea is to stop it from spreading before it becomes untreatable. We found that these drugs slowed the spread of cancer, but we’re hoping that we’ll find something that will essentially stop the spread of cancer.”

Jayatilaka and Wirtz are continuing to examine additional therapies that could potentially block both tumor growth and metastasis in different cancers, including breast, ovarian, and pancreatic. The team sees its treatment someday being used in tandem with conventional cancer therapies, such as surgery, radiation, and chemotherapy, with the promise of eliminating tumors—or at least blocking them before they spread.

city to suburbs
Illustration above by On On Lao; Portrait to the left by Caroline Andrieu

Johns Hopkins researchers have discovered that cancer metastasizes when conditions inside a primary tumor become too cramped, prompting the cells to seek new turf.

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