Scientists have uncovered a molecular key that breast cancer cells use to gain access to bone marrow, where they hide from the effects chemotherapy or hormonal therapies. The results of the mouse studies are published in Science Translational Medicine.
Not only have the researchers managed to prevent the cells from using this escape tactic, but they have succeeded in flushing the cells out into the bloodstream, where they can be targeted for destruction.
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The results of the study, by researchers at Duke University in Durham, NC, provide clues about ways to stop breast cancer from coming back after it has apparently been defeated once.
Senior author Dr. Dorothy A. Sipkins, associate professor in the Division of Hematological Malignancies and Cellular Therapy at Duke, explains that treating breast cancer early can leave the patient with no sign of disease.
However, up to 15 years later, the cancer resurfaces, most commonly in the bone.
According to the authors of the current mouse study, in this type of breast cancer, cells travel through body tissues and blood, looking for blood vessels in bone marrow that contain the molecule E-selectin.
The cells have a key. On their surface, they have molecules that bind to E-selectin. They use this key to enter the bone marrow. There they stay, inactive.
But years later, they reactivate, causing metastatic cancer. There is no cure for this.
Bone marrow biopsies from patients with breast cancer indicate that these cells, or micrometastases, are moving around from the very earliest stages of the cancer, traveling out of the breast tissue and into the bone marrow.
The researchers suggest that if they can find a way to inhibit E-selectin, this could stop the cells from getting into the bone and reappearing as metastatic cancer.
When they used an E-selectin inhibitor called GMI-1271 in mice, this stopped the breast cancer cells from entering the bone marrow. GMI-1271 is now being investigated in human clinical trials.
The team also managed to flush the cells out of their hiding places in the bone marrow and back into circulation by using plerixafor.
Once back in circulation, they should be more vulnerable to attack by the immune system, hormone treatment, or chemotherapy.
Plerixafor is used in human donation of bone marrow, because it pushes stem cells into the bloodstream, where they can be harvested.
“We are hopeful that by understanding how these breast cancer cells migrate through the body and what their life cycle is, we can discover ways to make them more vulnerable and treatable.”
Dr. Dorothy Sipkins
The researchers hope their findings might eventually lead to new treatments for breast cancer, if further research confirms the findings.
Treatment that intervenes at the molecular level could stop the dormant cells from digging in and causing a future relapse.