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Fred Hutchinson Cancer Research Center’s Dr. Kevin Cheung, a metastatic breast cancer translational researcher, has received a $4.1 million Department of Defense Breast Cancer Research Program “Era of Hope” Scholar Award. The award, which includes indirect costs, will fund his research for four years.
The DOD’s Breast Cancer Research Program is the second-biggest funder of breast cancer research in the U.S. Its Era of Hope Scholar Award encourages high-impact, collaborative research, particularly among innovative young researchers.
“This is a transformative award,” said Cheung, whose laboratory focuses on the cellular and molecular biology of tumor-cell clusters and how they drive metastatic disease. “I am excited by the flexibility this funding provides my lab to aggressively chase down the most exciting and impactful questions.”
According to the American Cancer Society, metastatic breast cancer is projected to kill 41,400 women this year. Cheung believes this number can be greatly reduced by focusing on tumor-cell clusters and the processes by which they “seed” the body for metastasis.
“Mounting experimental and clinical evidence suggests that tumor-cell clusters are potent metastatic seeds,” he said. “Pound for pound, compared with individual tumor cells, tumor-cell clusters have superior metastatic potential and drug resistance.”
Yet, how tumor cells cooperate to promote metastasis and therapy resistance is not known, Cheung said. His research will investigate these unknowns: What signals enable their superior survival compared with single cells? What allows for their entry into the circulation? And how do different tumor cells within clusters fuel drug resistance?
“By tackling the metastasis problem in this way — as a problem of synergy between tumor cells — we hope to gain insight into new therapies, biomarkers and monitoring technologies to extend survival in metastatic breast cancer patients,” he said.
Cheung’s grant will be used to pursue the following research goals:
- Develop a new therapy to prevent growth of micrometastases by targeting hard-to-reach signaling compartments. Cheung’s lab is currently investigating the unique protein signals produced by tumor-cell clusters, which are key to the cancer’s survival and proliferation. By interrupting these clusters’ signaling or “conversations,” he hopes to block the metastatic process.
- Discover imaging and secreted protein biomarkers at the time of initial breast cancer diagnosis that identify which patients are at risk of cluster-based dissemination. Working with breast radiologists and pathologists, Cheung will create a biobank of untreated, or “naïve,” breast cancer tumors to discover imaging and protein biomarkers that predict which patients are at highest risk for developing metastasis.
- Monitor micrometastatic drug resistance by rapidly cultivating circulating tumor cells, or CTCs, from metastatic breast cancer patients. Using new technology developed in his lab, Cheung and colleagues will create CTC-derived organoids from metastatic breast cancer patients and then use these models to predict the emergence of drug resistance.
This grant marks the second time Cheung has received funding from the DOD’s Breast Cancer Research Program.
“It was game-changing for me to receive their postdoc award in 2012,” he said. “Their funding support gave me the freedom to develop the initial research findings that would help me launch my laboratory at the Hutch. And looking back, this Era of Hope award reflects on that investment. Looking forward, I see it as my responsibility to make a good return on this new investment for our breast cancer patients.”
Cheung will collaborate with a handful of researchers on this project, including pathologist Dr. Peggy Porter, epidemiologist Dr. Kathi Malone, neurosurgeon and brain cancer researcher Dr. Eric Holland, and translational researcher Dr. Jason Bielas, all of Fred Hutch; University of Washington radiologists Drs. Savannah Partridge and Habib Rahbar, and molecular biologist Dr. Alana Welm of Huntsman Cancer Institute.
“This is a team effort,” Cheung said of his research collaboration. “What we want to do is use our combined clinical, scientific and technical prowess to transform insights about tumor-cell clusters into specific, clinically useful ways to improve outcomes in patients.”
He was also quick to acknowledge the help of breast cancer patient advocates Lynda Weatherby and Rebecca Seago-Coyle.
“They were instrumental in shaping how I put together this project,” he said. “I owe a lot of my success to them, and their continued insights will be critical as we move forward on this project.”
