Cyrus Ghajar, PhD, a metastatic breast cancer researcher at Fred Hutchinson Cancer Research Center, has received a $4.1 million Department of Defense Breast Cancer Research Program (BCRP) “Era of Hope” Scholar Award.
The Department of Defense’s BCRP is the second biggest funder of breast cancer research in the United States. Its Era of Hope award encourages high-impact, collaborative research, particularly among young, innovative researchers.
Dr. Ghajar is the Director of the Laboratory for the Study of Metastatic Microenvironments (LSM2), which is housed within the Translational Research Program in Fred Hutchinson’s Public Health Sciences Division. The LSM2 studies how microenvironments within distant tissues influence dormancy, drug resistance, and the reemergence of disseminated tumor cells. He will use the funds to research ways to prevent breast cancer metastasis by treating dormant disseminated tumor cells.
Dormant Tumor Cells as the Root of Recurrence
Metastatic breast cancer claims 40,000 lives a year; it’s estimated that 30% of all breast cancer cases will become metastatic. Interestingly, 20% of these cases will not emerge until a decade following therapy.
“The hypothesis is that these cells—which have left the breast and are in other organs, basically sleeping—eventually wake up,” he said. “When women relapse 7 or 10 years after treatment, these dormant cells are likely the root of recurrence.”
For this work, Dr. Ghajar has teamed with other Fred Hutchinson researchers, as well as investigators at Harvard Medical School and at the University of Colorado, Denver. Dr. Ghajar also has involved two local breast cancer patient advocates on this project.
Dr. Ghajar is investigating two different paths for dealing with these dormant disseminated tumor cells: keeping them asleep and inactive, or destroying them altogether.
“Basically, we are hedging our bets. You might be able to keep these cells asleep forever, but this carries an inherent risk, because you are leaving these ticking time bombs in your body. Perhaps we can mitigate this with a strong enough ‘sedative,’” he said. “But just in case, we also have ways we think will allow us to specifically get rid of them.”
According to Dr. Ghajar, the phenomenon of tumor dormancy has not been the subject of much study over the years. As a result, “we don’t really know a whole lot about these cells in terms of what puts them to sleep and what wakes them up,” he said.
“You can have a cell with oncogenic mutations, but if the microenvironment around the cell is telling it to behave, it will,” he said.
Dr. Ghajar found that single breast cancer tumor cells can exist peacefully on the blood vessels of various organs for months. However, if the blood vessel is disrupted—which inflammation and other processes can bring on—the cells will wake up and begin to form tumors.
“This grant is leveraging that finding,” he said. “We want to identify factors that keep the cells asleep, and we’re going to try to systematically reinforce those cues in an attempt to prevent metastasis. We’re also going to profile the outside of the blood vessel and figure out if there are molecules that uniquely mediate chemo resistance. We want to see if there are interactions we can disrupt that would make dormant cells die when patients are given chemotherapy.”
Finally, Dr. Ghajar has created a three-dimensional, laboratory-based breast tumor model that will allow his team to target sleeping tumor cells in hopes of destroying them—and provide a lasting cure for patients with cancer. ■