Attacking cancer cells where they hide
Like the gangsters in the B movie escaping from the police, sometimes cancer cells escape. They avoid capture (avoiding the surgeon’s knife) or death (the surviving chemotherapy drugs) and find a place to hide to cool their molecular heels off until the heat is turned off. And when they come out of their den, months or years later, these cells may be stronger than before, and they may create metastases that are more resistant than the original cancer. In an article published in May, Duke University researchers said they have identified two proteins in lab mice that allow hormone-positive breast cancer cells to escape, attach to the bone marrow, and hide from treatment. “We now know how they get in,” Duke’s Dr. Dorothy A. Sipkins says, in announcing the results. “We have also identified an important mechanism that allows them to remain firmly established in the bone marrow.”
When breast cancer cells spread
Breast cancer cells are notoriously nomadic and are known to travel and settle in the bones, brain, liver and lungs. In some cases, cancer cells can escape from the primary tumor before the patient is diagnosed. These cells can remain dormant or grow slowly in their lair, even when a patient goes through months of treatment and then doctors are told they haven’t found any signs of cancer. “Because these cells grow so slowly, it can take a long time before you realize that someone has had metastatic disease,” says Cynthia Lynch, MD, a medical oncologist at our hospital near Phoenix.
The Duke researchers say that some of these metastatic cells are looking for the E-selectin molecule, which is often found in the bone marrow. Cancer cells bind to E-selectin, allowing it to enter the marrow. There, another protein called CXCR4 allows cells to nest in the marrow, where they can hide for years. The E-selectin inhibitor GMI-1271 can prevent metastatic cells from entering the bone marrow. The researchers also believe that the drug plerixafor (Mozobil® ) , which can be used to treat multiple myeloma and non-Hodgkin’s lymphoma, could act as a CXCR4 blocker and kill hidden cells, exposing them to treatment. “By understanding how these breast cancer cells migrate through the body and their life cycle, we hope that we can discover ways to make them more vulnerable and treatable,” says Dr. Sipkins, lead author of the article. Scientific translational medicine .
This ability to hide and evade treatment makes it necessary for breast cancer patients to stay on treatments like tamoxifen (Nolvadex®) or an aromatase inhibitor that blocks hormones, even after tests show that your body no longer has evidence of cancer, says Dr. Lynch. Inactive or slow-growing breast cancer cells do not always respond to chemotherapy, which can have difficult side effects. And hormone therapy can take up to a decade’s commitment. “It’s a long time to take a drug that also has side effects,” he says.
Some patients who experience treatment fatigue also have difficulty staying on their cancer treatment regimen. “Sometimes patients think this is because their prognosis is so good that they may be able to get rid of it without undergoing hormone therapy,” he says. “But we see that in hormone-positive breast cancer, the risk of recurrence is about the same in years five to 10 as it is in years one to five. I say this to patients, not to scare them, but because we have medications that can reduce hormone production and have The effect is very powerful in reducing the risk of recurrence.”
In the search for better treatments and prevention strategies, scientists are learning more about how cancer grows and survives, even in the harshest environments. This blog is part of an occasional series called How Does Cancer Do It? Designed to highlight recently discovered cancer-related behaviors that add to our growing understanding.
Learn more about advanced treatments for breast cancer.