So often, a cancer diagnosis comes shrouded in mystery, the malignancy’s precise cause unknowable. But for some cancers, the cause is clear: Certain infectious agents, from human papillomavirus to the bacterium Helicobacter pylori, can directly or indirectly lead to cancer. As many as one in five cancer patients worldwide can trace their disease to a pathogen.
But the source of these cancers may also be their undoing. Knowing exactly what prompts tumor development allows scientists to focus their prevention and treatment research on a specific target.
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Fred Hutchinson Cancer Research Center is taking advantage of this opportunity and tackling the problem of pathogen-associated malignancies head-on with a focused, collaborative approach. The Hutch’s new Pathogen-Associated Malignancies Integrated Research Center will capitalize on deep experience in basic cancer biology, global oncology, immunotherapy, vaccine development, and more to seek out improved treatment and prevention strategies.
“Each year, 14 million people worldwide are diagnosed with cancer, and up to 20 percent of those cancers are caused, directly or indirectly, by viruses and other pathogens,” said Dr. Gary Gilliland, president, and director of Fred Hutch. “Our goal is to seize the opportunity we now have to lead the way in eliminating that burden — and to advance cures for all cancers.”
Dr. Denise Galloway, whose research helped pave the way for the cancer-preventive HPV vaccine, will direct the new center.
“Not only will [the integrated research center] help us learn more about how to prevent and treat pathogen-associated malignancies and how specific pathogens trigger cancer, but these studies will provide insights that are applicable to the understanding, prevention, and treatment of a wide range of cancers,” even those not directly related to pathogens, Galloway said.
Galloway, who also holds a Fred Hutch 40th Anniversary Endowed Chair, is the ideal scientist to lead an integrated effort to tackle pathogen-associated cancers, said Dr. Bruce Clurman, executive vice president and deputy director of Fred Hutch.
“There are very few investigators in the world who have the breadth of her knowledge and vision when it comes to understanding the interactions between oncogenic pathogens and hosts in the development of cancer,” Clurman said. Galloway’s work has ranged from “world-class” basic cancer biology to translational, real-world applications such as the development of the HPV vaccine, he said.
HPV causes not only cervical cancer, but most anogenital cancers and a growing proportion of head-and-neck cancers, making the HPV vaccine a potentially lifesaving intervention against a number of diseases. Galloway headed research teams that definitively linked HPV to these tumor types, and her laboratory created the virus-like particles based on HPV proteins on which the vaccine was built. She collaborated in the proof-of-principle clinical trial that showed a vaccine against HPV 16 actually protected against infection with that strain of the virus, known to be one of several strains linked to cancer.
In 2011, the American Association for Cancer Research recognized these remarkable contributions by awarding the Fred Hutch and University of Washington team headed by Galloway the fifth annual AACR Team Science Award.
As proud as Galloway is that her research contributed to a lifesaving cancer-preventive vaccine, she knows that studying how viruses and other pathogens upend normal cellular processes can provide insights with the potential to benefit all cancer patients.
“Many of the [molecular] pathways that are altered in all cancers were identified because viruses interact with them,” she noted. Viruses trade on snippets of genetic material to wreak havoc inside cells, and by studying “these clever tiny bits of nucleic acid,” researchers can pinpoint molecular processes that turn out to be commonly important in other cancers, Galloway said.
Furthermore, she believes that now is an opportune time to capitalize on the confluence of technological improvements that allow scientists to clearly link pathogens to tumors and advances across diverse research areas, such as immunotherapy, that are enhancing efforts to develop better ways to diagnose, treat and prevent cancer.
Galloway is just one of several world leaders in pathogen-associated cancers at the Hutch, said Clurman. Her peers in the field include Dr. Nina Salama, a renowned expert in H. pylori, the bacterium associated with ulcers and stomach cancer; and Dr. Edus “Hootie” Warren, an immunologist who researches Burkitt lymphoma, a cancer common in sub-Saharan Africa that is commonly linked to infection with Epstein-Barr virus, or EBV. Salama holds the Dr. Penny E. Petersen Memorial Chair and developed some of the first genomic tools to identify H. pylori strains most associated with stomach cancer.
Warren also heads Fred Hutch Global Oncology, which grew out of collaborations between Hutch researchers and Ugandan scientists examining the role of viruses such as Kaposi sarcoma herpesvirus, EBV, HPV and HIV in the development of cancer. In 2008, the scientific partnership was formalized in the UCI/Hutchinson Center Cancer Alliance.
For more than a decade, Hutch global oncology researchers have delved into the biology of pathogen-associated cancers and have become experts at assessing the barriers to providing cutting-edge cancer care in low-resource settings — and how to overcome them. The close connections between Fred Hutch Global Oncology and the Pathogen-Associated Malignancies IRC helps scientists identify which infectious agents and related cancers most impact human health around the world — that is, where opportunities exist for research to make the biggest difference for patients. Collaboration between these experts will also enhance their ability to test strategies for delivering new therapies, diagnostics and approaches to prevention.
Galloway and Hutch leaders also envision that the research conducted through the new center will inform and be informed by another area of Hutch strength: immunotherapy. Immunotherapy harnesses components of the immune system to fight cancer, and Hutch scientists have long been pioneers in the field, forging living therapies that are helping to save lives.
“Many of the ways that we initially deal with pathogen-associated cancers are likely to be through immunotherapeutic approaches,” Clurman said.
Fred Hutch launched its first IRC, dedicated to immunotherapy research and development, just last year. Understanding how the immune system responds to cancer-causing pathogens — and how they can circumvent its defenses — will improve immunotherapeutic approaches to treating cancer, including cancers caused by infections.
Technological advances have improved the speed at which scientists can pinpoint immunotherapy targets and develop new therapies based on those targets; viruses that persist in host cells may be uniquely vulnerable to this approach.
Merkel cell carcinoma is an ideal example of how a confluence of new technologies and progress in different fields of research can lead to lifesaving advances. In 2008, researchers capitalized on improved research tools to definitively link Merkel cell polyomavirus to Merkel cell carcinoma, or MCC, a particularly aggressive skin cancer. Since then, Galloway and Dr. Paul Nghiem, a world expert in MCC at the University of Washington and Fred Hutch, have developed a test to predict recurrence of the rare disease, and Nghiem helped pioneer the use of immunotherapy for patients with this cancer. The latter, a drug that helps unleash the immune system, earlier this year was approved by the Food and Drug Administration to treat MCC. Now Nghiem and colleagues at the Hutch are also exploring ways to use MCC patients’ own immune cells against their tumors.
Pathogens can lead to cancer in a variety of ways. HPV directly causes cancer in some patients by inactivating molecules that suppress tumor development and by increasing DNA mutations. Hepatitis B and C act indirectly by promoting cirrhosis, or chronic liver damage, which predisposes infected people to develop liver cancer. And HIV can raise the risk of a range of pathogen-associated cancers by wreaking havoc on the immune system and its ability to defend against infection.
But not everyone infected with these viruses — or other pathogens linked to cancer — will develop tumors. Clarifying why certain infections don’t lead to cancer the vast majority of the time is just as important as discovering why they sometimes do, and exactly what to do about it.
Galloway knows the power of team science to tackle the ins and outs of a disease and produce tangible benefits to patients. Basic scientists, epidemiologists, biostatisticians and clinicians all contributed to the successful examination of HPV’s ties to cancer.
She attributes Nghiem and his colleagues’ rapid success in discovering a successful MCC therapy to his dedication to patients with MCC and his drive to recognize the potential in other areas of research, such as immunotherapy. Similar connections across scientific disciplines could make all the difference for other pathogen-associated malignancies.
Advances “really need people to be the driver, to nucleate those connections,” Galloway said, and the new Integrated Research Center is designed to facilitate and strengthen those partnerships. The goal for Galloway is to extend similar successes to other pathogen-associated malignancies.
“You know, we had a great success with HPV,” said Galloway. “I would like to see similar successes across the spectrum of cancers caused by infection.”
Sabrina Richards, a staff writer at Fred Hutchinson Cancer Center, has written about scientific research and the environment for The Scientist and OnEarth Magazine. She has a PhD in immunology from the University of Washington, an MA in journalism and an advanced certificate from the Science, Health and Environmental Reporting Program at New York University. Reach her at srichar2@fredhutch.org.
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