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Cyrus Ghajar, PhD
Associate Member, Division of Public Health Sciences
Fred Hutchinson Cancer Research Center
Seeking to understand how the environment at distant organ sites is changed to support metastatic cancer.
Laboratory studies are conducted to design treatments to target ciculating tumor factors and sensitize dormant tumor cells to chemotherapy.
These studies may lead to a new strategy to make prevention of metastasis a reality for breast cancer survivors.
Metastasis is a complicated, multistep process that requires the tumor cells to break away from the tumor, enter the circulation (early metastasis) and become established at a distant site (late metastasis). In the early phase, a tumor cell can lie dormant until awakened by some other event and progress to become a new tumor. Studies by Dr. Ghajar have uncovered similarities in the signaling events that promote both tumor cell dormancy early in metastasis, as well as tumor establishment at the new site in late metastasis. His current work is focused on targeting these pathways to prevent metastasis.
Full Research Summary
Before metastasis occurs, the site of metasasis (e.g., the lung, bone marrow or brain) has to be “primed” to support the growth of the tumor, since the distant site is an unfamiliar environment to the tumor cell.
One way tumor cells do this is to send out small packages called exosomes that reach sites of future metastases to create a habitable environment to support metastatic growth. Therefore, targeting exosomes or restoring the natural environment at the potential site of metasasis may prevent metastases from occurring.
Another factor that adds to the risk of metastasis is the phenomenon of tumor cell dormancy, i.e. breast tumor cells that have left the breast lie dormant in other tissues where they are hidden from usual screening methods and are resistant to cancer treatments.
We know very little about what keeps these dormant cells sleeping or what wakes them up to form a new tumors years or even decades after treatment.
Previous work from Dr. Ghajar and his collaborators, BCRC investigator, Mina Bissell and David Lyden (Weill Cornell Medical College) uncovered commonalities between these two events, where the same pathways help exosomes find the distant sites for metastasis and also keep dormant tumor cells alive despite therapy.
By studying this signaling, Dr. Ghajars's research may identify new strategies to prevent early metastases by targeting exosomes and sensitizing dormant breast tumor cells to chemotherapy. This approach could significantly augment standard of care and make metastasis prevention a reality for breast cancer survivors.
Dr. Cyrus Ghajar is an associate member in the Fred Hutchinson Cancer Research Center's Division of Public Health Sciences. He studied bioengineering at the University of California, Berkeley before moving on to Stanford University to earn an MS in materials science and engineering. He culminated his studies at the University of California, Irvine where he received his MS and PhD in biomedical engineering. He now directs the Laboratory for the Study of Metastatic Microenvironments (LSM2) in the Hutch’s Translational Research Program. Broadly, he is interested in how “foreign” tissue microenvironments influence the behavior of disseminated tumor cells (DTCs). Specifically, his laboratory is working to understand how tissues regulate DTC dormancy, how the dormant niche contributes to therapeutic resistance, and how local and systemic changes impact the dormant niche and foster DTC re-emergence. His belief is that solving these puzzles will allow the development of therapeutic regimens that eradicate dormant DTCs before they can develop into full-blown metastases.