Two early-career investigators at Fred Hutchinson Cancer Researcher Center have received grants that will fuel their research into metastatic breast cancer. Dr. Erica Goddard, a postdoctoral research fellow in Dr. Cyrus Ghajar’s Laboratory for the Study of Metastatic Microenvironments, won a Breakthrough Fellowship Award from the Department of Defense Breast Cancer Research Program. She will receive a total of $528,000 over three years.
Dr. Mark Headley, an immunologist who studies the cellular and molecular dynamics behind tumor metastasis, received an Early Career Investigator Award from METAvivor, a nonprofit organization dedicated to funding research for stage 4 metastatic breast cancer.
For most breast cancer patients, years or even decades can separate initial treatment and metastasis.
Why the lag?
Mounting evidence suggests that these metastases arise from tumor cells that spread to distant organs even before diagnosis, but they lie dormant until triggered to reawaken. Goddard will use her award to try and reveal the mechanisms by which breast cancer cells can sleep undetected for years and then wake up.
Goddard’s ultimate goal is to use those lessons to develop immunotherapies that can eliminate dormant tumor cells. T cell-based immunotherapy has proved itself in the clinic as a potent tumor-killing force. But little is known today about the relationship between T cells and dormant breast cancer cells. Do these sleeping cells actively evade the immune system? Are circulating T cells able to find and kill them?
To find out, she plans to test two types of immunotherapy: T-cell receptor (TCR) and chimeric antigen receptor (CAR) T-cell therapies. At a minimum, Goddard said, her research could greatly expand our understanding of how dormant tumor cells escape immune killing. It could also lay the foundation for future studies that may bring TCR and CAR T cells into the clinic for breast cancer survivors.
The translation of these T-cell immunotherapies to breast cancer —and specifically to the window of breast cancer dormancy —has the potential to impact tens of thousands of breast cancer patients annually, Goddard said.
Headley and his lab in the Clinical Research Division seek to understand how immune cells can be both friend and foe during metastasis. Some immune cells work hard to detect and defend against cancer. But others actively serve the tumor, helping it survive and thrive.
The monocyte is a type of immune cell that can play both roles. The reasons how and why it acts like a double agent are poorly understood, Headley said. But he’ll use his METAvivor grant to fund several studies that aim to define how monocytes contribute to metastasis and their influence on outcomes and survival.
These studies will harness a new tool that Headley’s lab developed. The tool, a monocyte-deleting antibody, can help detail how monocytes function at every step of metastasis. Headley’s lab will also use an approach called single-cell RNA sequencing that can not only help investigate how monocytes evolve during metastasis, but how they impact the networks of cells around them inside the metastatic tumor.
Headley ultimately hopes his research lays the groundwork for a new class of therapies that boost the monocyte’s innate ability to battle metastasis — and block its traitorous tendencies.
Jake Siegel is a former staff writer at Fred Hutchinson Cancer Center. Previously, he covered health topics at UW Medicine and technology at Microsoft. He has an M.A. from the Missouri School of Journalism.