Fred Hutch researchers root out sleeping breast cancer cells to stop metastasis

In In The News by Barbara Jacoby

By: James Thorne


Researchers at the Fred Hutchinson Cancer Research Center led by Dr. Cyrus Ghajar recently uncovered promising new science in the battle against metastatic breast cancer. Their findings, published today in Nature Cell Biology, show that it’s possible to destroy cancer cells that can hide for years in people’s bone marrow.

Chemotherapy is often effective at destroying fast-growing cells, but there’s a problem: cancer cells can go dormant and avoid chemotherapy, only to return years later. In patients with the most common form of breast cancer, dormant cells can avoid detection only to wreak havoc again after many years. This process, known as metastasis, is responsible for more than 90 percent of the deaths associated with breast cancer.

“What were those cells doing the entire time? Well, what we know now is that cells leave the breast very early during tumor progression. They can lay dormant in these organs for a very, very long period of time,” Ghajar told GeekWire.

Both active and sleeping cancer cells can hide among blood vessels in bone marrow, using what’s called survival signaling as protection. Ghajar wanted to know if it would be possible to remove the protective signaling and kill the cells with chemotherapy.

Here’s the basic process that the team followed over the course of four years:

  • First, they identified the genes and proteins involved in the protective process that sheltered cancer cells in blood vessels.
  • That detective work led them to molecules that bind to integrins, which are proteins involved in cell signaling.
  • The team then tested different integrin inhibitors and identified two that could “turn off” the protective signaling.
  • Finally, they treated the protected cancer cells with the inhibitors and chemotherapy. They tested both mice models and cells in dishes containing blood vessels and bone marrow, which simulated the conditions in which cancer cells are known to hide.

The plan worked. When they combined the inhibitors with chemotherapy on the mice, around 94 percent of the dormant cells died. The rate at which cancer metastasized dropped from 70 percent with chemo alone to 22 percent with the combined treatment.

Ghajar said the next step is to create a human version of the antibody and progress toward a clinical trial. At this point, any treatment would be a first. “There’s not a single drug currently that selectively targets dormant, disseminated tumor cells,” said Ghajar.

But a clinical trial could take years if it happens at all. Ghajar admits the chances of translating a successful mice model to a human treatment are “dismal,” and the cost to do so can be up to $1 billion or more.

Either way, Ghajar and his team showed that dormant cancer cells can be killed with chemotherapy, which goes against conventional wisdom that chemo only attacks quickly replicating cells. Critically, this can be done without “waking up” the dormant cancer cells.

Early funding for Ghajar’s research came from the Fred Hutch and the Cuyamaca Foundation. The Department of Defense gave the project more than $4 million as part of its Era of Hope award for breast cancer research.

Ghajar hinted at other major initiatives that Fred Hutch researchers are pursuing.

“We’ve really been making a big effort to take chemotherapy out of the equation,” he said. “That’s one huge project that is underway, and we have some kind of promising leads right now.”