Photo by Robert Hood / Fred Hutch News Service
Dr. Denise Galloway has received one of the National Cancer Institute’s 2017 Outstanding Investigators Awards. The award recognizes established scientific leaders who are making significant strides not only in understanding cancer but in creating techniques that could lead to research breakthroughs in the future. Galloway is the first Fred Hutchinson Cancer Research Center scientist to receive an Outstanding Investigator Award, which was introduced by the NCI two years ago.
The new award provides a little more than $7 million over seven years. Galloway, who directs the Pathogen-Associated Malignancies Integrated Research Center and holds a Fred Hutch 40th Anniversary Endowed Chair, will use the support to pursue deeper insights into two viruses that cause cancer: human papillomaviruses (HPV), certain strains of which can cause cervical, anogenital and head-and-neck cancers; and Merkel cell polyomavirus (MCPyV), which can lead to Merkel cell carcinoma (MCC), a rare but aggressive form of skin cancer.
Galloway’s work on both viruses has already influenced public health and patient care. She helped lay the groundwork for the cancer-preventive HPV vaccine and, in collaboration with Hutch colleague Dr. Paul Nghiem, developed a clinical test for MCPyV that could help detect very early relapse of Merkel cell cancer.
The new award will allow her to extend those accomplishments by taking a high-risk, high-reward approach to research that other grants often limit.
“I feel very lucky,” said Galloway of receiving the award, which, unlike many grants that require yearly renewal, provides a guaranteed funding source for seven years. “[The Outstanding Investigator Award] gives you freedom.”
New tools and new insights
Many of the questions that Galloway will ask with that freedom will require her team to develop new research tools, including new preclinical models for studying these viruses in the lab. As HPV and MCPyV destabilize normal cells, these cells pick up DNA errors on their way to becoming cancer cells — and certain errors are probably a critical part of this transformation, although it’s not currently clear which.
The new disease models will help Galloway tease out which DNA errors are central to cancer development and progression. She aims to use this knowledge to develop screening tests for cervical cancer that can distinguish between the HPV-triggered clusters of disorganized cells that will go on to become cancer and those that are benign.
Additionally, the models will make it possible to test new immunotherapies against HPV- and MCPyV-caused tumors in the lab before advancing the best candidates to patients.
“We need to develop new therapies for cervical cancer. The scientific community has not moved forward on that front for quite a while, and I think that understanding … where these [virally infected] cells might be particularly vulnerable could be exploited with new and targeted therapies,” Galloway said.
Integrating basic insights with patient care
Thanks to Nghiem and Galloway’s collaboration, it’s already known that at least one immunotherapy can help patients with MCC. Their partnership led to a clinical trial testing the efficacy of an immune-boosting therapy in patients with a chemotherapy-resistant form of the disease. That therapy became the first drug approved by the FDA to treat MCC.
An unexpected MCPyV protein prompts normal cells to take on cancer-cell characteristics. How this process works is still poorly understood — but that may be a window of opportunity.
“If you can figure out the pathway [that MCPyV alters], you might be able to figure out a target,” she noted. Supported by her new grant, Galloway intends to glean further insights that will aid in the development of therapeutic vaccines against this cancer.
Her team is also working to learn more about how our bodies respond to the HPV vaccine and what this can teach us about how improve it, how to best administer it, and who can benefit.
“When you think about a schedule for vaccinating, it ought to be informed about what type of [immune] memory responses you make,” said Galloway.
Galloway’s work has long bridged basic and translational research. She contributed to the research that definitively linked HPV with cancer, and her team was among the first to show that an HPV protein could self-assemble into structures that mimic the full virus well enough to form the basis of a vaccine against the high-risk strains linked to cancer. Using these virus-like particles, Galloway’s team was among the first to develop tests to measure HPV infection.
She also collaborated with scientists at the University of Washington who charted the prevalence of HPV in young men and women — necessary insights to assess the effectiveness of the vaccine. The Outstanding Investigator Award will enable Galloway to build on this foundation while pursuing scientific leads in a more nimble fashion than allowed by most grants.
“It allows you to be more creative,” said Galloway.
Sabrina Richards, a staff writer at Fred Hutchinson Cancer Research Center, has written about scientific research and the environment for The Scientist and OnEarth Magazine. She has a Ph.D. in immunology from the University of Washington, an M.A. in journalism and an advanced certificate from the Science, Health and Environmental Reporting Program at New York University. Reach her at firstname.lastname@example.org.
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