The map apps on our mobile phones don’t just show us the route, they can guide us street by street — even building by building. It took years of data gathering, development and analysis to give us mapping with this much precision. Researchers believe that precision oncology holds similar potential: To use mountains of data and cutting-edge computational tools to help each cancer patient — and their clinicians — better navigate their unique disease.
A transformational commitment by Stuart Sloan and his wife Molly Sloan of $78M to establish the Stuart and Molly Sloan Precision Oncology Institute at Fred Hutchinson Cancer Center aims to help researchers fulfill the early promise of this data-driven approach. The largest single gift in Fred Hutch’s 47-year history will go toward the recruitment of an institute director and scientific programs that will aim to spark innovative new discoveries, and a new building to house the laboratory space and enabling technologies critical to those discoveries.
“The Sloans' generous gift will help Fred Hutch establish one of the world’s premier precision oncology centers that will bring together our very best basic science, data science, disease-oriented translational science, science of cancer prevention and understanding of the immune system,” said Dr. Thomas J. Lynch, president and director of Fred Hutch and holder of the Raisbeck Endowed Chair. “This gift is going to allow us to build a program that will drive innovation at Fred Hutch for the next 20 to 30 years.”
The donation grew out of Stuart Sloan’s longstanding relationship with Fred Hutch. In 2013, Sloan was the founding sponsor for the fundraising event Obliteride, which he cycles in every year. His commitment was inspired by Fred Hutch as the birthplace of bone marrow transplantation, a Nobel Prize-winning advance that has been used to treat 1.5 million people with blood cancer and other diseases, and the center’s history as one of the earliest established National Cancer Institute-designated cancer centers.
The Sloans were further motivated by the recent merger between Fred Hutchinson Cancer Research Center and Seattle Cancer Care Alliance to form Fred Hutchinson Cancer Center, uniting comprehensive care and advanced research to provide the latest treatment options and accelerate discoveries that prevent, treat and defeat cancer and infectious diseases worldwide. Fred Hutch is an independent, nonprofit organization that also serves as UW Medicine’s cancer program.
The Stuart and Molly Sloan Precision Oncology Institute will capitalize on the closer connection between lab science and clinical care facilitated by the merger and encourage integration of precision oncology efforts with Fred Hutch’s strengths in data science and immunotherapy.
“The new institute will be dedicated to discoveries, a big part of what Fred Hutch is all about,” Lynch said.
“Cancers are driven by unique genetic changes within the cancer,” Lynch said. “They're influenced by the microenvironment that the cancer lives in — including the microbiome, including immune cells, including the cells that we all bring to the table that are not cancerous. Understanding all of these factors is really what precision oncology is all about.”
Lynch should know. In 2004, he helped usher in the modern era of precision oncology, in which key genetic changes within tumors can be used to tailor treatment, when he was part of the team that discovered that lung tumors with certain mutations in the EGFR gene, which encodes a growth-promoting molecule, are more sensitive to treatment with EGFR inhibitors like gefitinib and erlotinib. These drugs dramatically slow the growth of lung tumors with the right EGFR mutations.
An even more dramatic example of what precision oncology can accomplish is imatinib, better known as Gleevec. This inhibitor targets the gene fusion behind chronic myelogenous leukemia, and gives someone with CML the same life expectancy that person would have if they didn’t have CML.
The list of mutations and genes that researchers have linked to prognosis and treatment response in various types of cancer continues to increase. When a person is diagnosed with cancer nowadays, their tumor’s DNA is assessed for a panel of mutations that may alter prognosis or guide treatment. Oncoplex, the panel developed by the University of Washington, tests more than 350 genes for various types of mutations. But relatively few cancers are driven by a single genetic change. With 30 trillion cells in the human body, a massive amount of research remains to catalog which collections of genetic mutations are tied to cancer.
As technologies for digging into tumor characteristics — from DNA to proteins to the tumor microenvironment — have advanced, our appreciation for cancer’s complexities has advanced as well.
“When I trained 30 years ago, we thought there were 20 cancers: One cancer for every organ system, and some cancers, like lung, had small cell and non-small cell. We now know that there are hundreds of cancers, all driven by different [genetic] patterns,” Lynch said. “Breast cancer is probably 20 diseases.”
A combination of factors, including genetic and metabolic factors, the microbiome and the tumor’s microenvironment of non-cancerous cells, such as immune cells, all collaborate to influence how the disease begins, grows, survives and responds to treatment. Now, said Lynch, understanding what patterns mean will be paramount. Precision oncology’s next phase will require novel ways of addressing a tumor’s molecular characteristics, immune microenvironment and microbiome.
We also need to find better ways of using the clinical information and treatments we already have to improve patient care. Dr. Eric Holland, a neurosurgeon and brain cancer researcher at Fred Hutch who directs the center’s Human Biology Division and Seattle Translational Tumor Research program, takes a big-picture view of precision oncology. His goal is to build the maps that patients and oncologists can navigate through to pinpoint the best treatment strategies.
He and his team are working to develop the computational tools, analytical techniques and visualization approaches that transform reams of tumor data from tens of thousands of patients into tumor landscapes, in which tumors cluster in neighborhoods dictated by key tumor and patient characteristics.
“You get little clusters of similar tumors. And then if your next patient lands in that landscape on this little island, then you know that patient probably has a tumor like their neighbors. And if they all respond well to a particular drug, then you can expect this patient will too.”
But getting there requires clearing significant hurdles. Collecting the full range of tumor information, plus clinical data like prognosis, survival time and treatment responses produces heaps of data — the Big Data that data scientists are wrestling with. Holland and scientists across the center are working on creative solutions to turn enormous amounts of data into recognizable tumor landscapes, as well as finding ways to safeguard, manage and visualize that much data.
Key to these efforts, and the future discovery efforts that the Stuart and Molly Sloan Precision Oncology Institute will make possible, is data science, said Dr. Jeff Leek, who is Fred Hutch’s new Chief Data Officer and holds the Orin J. Edson Endowed Chair.
Storing and analyzing a clinical measurement is becoming more challenging, Leek noted. And the technologies that enable us to collect comprehensive genetic information, or other types of information like radiologic data, from thousands of people produce terabytes or petabytes (about 1000 trillion bytes) of data that must be processed, modeled and used to generate predictions.
“But all these new tools are being developed in the [data science] field. It’s an exciting time to have this intersection of this computationally sophisticated machinery … and incredibly cool technologies for measuring the way that people respond to the treatment. That intersection is the coolest thing going right now," Leek said.
The Stuart and Molly Sloan Precision Oncology Institute will provide an opportunity to build a modern data science program that addresses current challenges with an eye to the future, he said: “It’s an exciting opportunity for someone like me to imagine from the ground up. … There have already been some incredible discoveries in precision oncology, but in pockets. The scaling up of these new revolutions in precision oncology is going to happen over the next 10 to 15 years.”
Data scientists won’t just be helping cancer scientists ferret out new treatment targets. The new institute will also be a home for researchers developing better, more personalized risk reduction and diagnostic strategies.
Genetic epidemiologist Dr. Ulrike Peters, who studies genetic risk factors for colon cancer and holds the 40th Anniversary Endowed Chair, works closely with computational biologists and biostatisticians. She examines inherited genetic differences which can increase or decrease someone’s risk for colorectal cancer.
“We have identified 250 genetic risk factors,” she said. “Each of them individually has a small effect, but because we have so many, they matter.”
She and her collaborators are refining a risk stratification tool, which uses key genetic differences to help determine how often a person should be screened for colon cancer.
It couldn’t be done without data science, she said.
Dr. Minta Thomas, a postdoctoral fellow on Peters’ team, is building a model that includes over a million genetic variants from over 100,000 colorectal cancer patients and 150,000 participants without the disease.
“Through machine learning approaches, we can really harvest more of the genetic data than just the risk factors we have identified, because there's more information in those large-scale data,” Peters said.
Dr. Alice Berger, lung cancer researcher
The Stuart and Molly Sloan Precision Oncology Institute will also help more researchers capitalize on the deep knowledge of the immune system and immunotherapy.
“Fred Hutch has this incredible history in immunotherapy, and now we're committing and deepening our background and track record in precision oncology to bring these two areas together,” Lynch said.
Fred Hutch pulmonologist Dr. Viswam Nair, who joined the center a few years ago, agrees.
“I came here to learn about immunology and apply that to my research,” he said. “I think about the Hutch not only as a cancer center, but as an infectious disease center. Not a lot of cancer centers have that dual mission. Because now immunology is the forefront of tumor treatment, we’re uniquely positioned.”
Recent immunotherapy advances have transformed care for some cancers — but many more patients stand to benefit. There’s a lot of potential to make immunotherapy more personalized, said Hutch pulmonologist Dr. McGarry Houghton, who studies lung cancer and leads the center’s Lung SPORE. Houghton also studies the role of the immune system in cancer.
“What we’re trying to get at is how you would use immune therapies to target individual cancers,” he said. For the most part, immunotherapies currently on the market don’t take into account unique mutations.
His team is working to develop a diagnostic package that can be used to analyze the genetic, immune and molecular makeup of a patient’s tumor all at once. The idea is to learn more about the immune response to tumors that so far haven’t responded to immunotherapy, and use that information to develop effective new therapies, more tailored to a patient’s individual tumors.
“The idea is to understand how the whole package is put together,” he said.
Lynch is cognizant of how the Sloans’ confidence in the center’s past discoveries and future potential inspired their support. Making strides against cancer, and being intimately involved in creating the next platform for looking for cancer cures, matter to Sloan, he said.
“With this gift, we want to expand the discovery and development of precision therapies for more cancers and bring hope to everyone who is unfortunately experiencing cancer,” Stuart Sloan said.
This doesn’t mean that researchers will stop combing tumor DNA for new risk markers or treatment targets. Dr. Alice Berger, who seeks to better understand the genetics of lung cancer and find new treatment targets for the disease, was initially inspired by Lynch’s pioneering work on EGFR. Her own work has shown that we have a lot left to learn about tumor genetics.
EGFR isn’t the only gene linked to lung cancer. Berger, who holds the Innovators Network Endowed Chair, recently received a National Institutes of Health MERIT Award to support her studies of RIT1, another gene that drives lung tumors in tens of thousands of people every year. Berger suspects that RIT1-driven tumors have vulnerabilities, which researchers can take advantage of, lurking within them. Her projects aim to discover and target them.
But she agrees that we need to consider the complexity of the genetic composition of tumors when developing tomorrow’s treatments.
“In lung cancer, there have been amazing advances in patient outcomes due to targeted therapies [like EGFR inhibitors] but it’s not good enough,” she said. “Most patients will ultimately see their tumors progress. We need to do better.”
Combining targeted treatments may be one way forward, Berger said, and they may also end up being less toxic.
“An area I’m excited about is combining targeted treatments with more immuno-targeted therapies,” Berger said. “In addition to our strengths in cancer prevention, our strength in cancer immunology really positions us in an exciting way to combine our understanding of the immune system with our understanding of how to target specific tumor genetics in effective ways.”
Other areas of opportunity in precision oncology include ensuring that treatments and risk-reduction strategies, new and old, are available to everyone. This is a core part of Fred Hutch's mission.
Peters is working to make that possible for the risk-stratifying tools that her team is developing with Hutch colleague and biostatistican Dr. Li Hsu.
“Our models currently predict really well in European populations,” she said. “They don’t do so well for African American, Hispanic and Asian populations. We’re trying to overcome that.”
Improvements will come from incorporating the genetics of people whose ancestry reaches to more parts of the world, and in new, ever-more sensitive technologies, like the ability to sequence the DNA in individual cells, Peters said.
Diagnostics, prevention plans and treatments must also become more cost-effective for patients, said Nair. He works to improve lung-cancer diagnostic and screening tools by identifying and integrating patient biomarkers.
“A lot of the things we do are extremely time-intensive, resource-intensive, skill and labor intensive, and they cost a lot. We need to figure out how to do it cost effectively,” Nair said.
The Stuart and Molly Sloan Precision Oncology Institute’s positioning is not merely metaphorical.
“Seattle is uniquely the best place to do this sort of thing because we sit at the intersection of a serious biotechnology hub and a serious computational and machine learning hub,” Leek said.
Fred Hutch’s South Lake Union campus sits blocks away from offices for Google Cloud and Amazon Web Services — and Microsoft’s Azure is just a few miles away. These cloud computing tools will be essential to storing and analyzing the massive amounts of data that will be needed to create the cancer landscapes that Holland, Leek and their colleagues want to map. The center’s neighbors also include biotech companies, like Fred Hutch spinoff Adaptive Biotechnologies, that use innovative computational approaches to accelerate our understanding of human health.
The Stuart and Molly Sloan Precision Oncology Institute Building will be located between Fred Hutch's newly expanded clinical space and current laboratory buildings. Reflecting the closer connections between research and clinical care made by the recent merger, the building will literally and figuratively connect scientists working on precision oncology from every angle.
“As Fred Hutchinson Cancer Center, we have the ability to approach solid tumors in a way we didn't have before,” Lynch said. “The ability to look at surgically resected tumors, to look at the microbiome, to look at the genetics of cancer, give us this ability to really rethink the possibilities of solid tumor oncology.”
Leek is also excited about what the new Fred Hutch makes possible.
“Bringing research and clinical practice closer together is a core component of a precision oncology program,” he said. “You need both a research arm that will make the discoveries and a clinical arm that will test and deliver those discoveries. If you only have one part of it, you only have one part of the revolution. Together, it’s really fertile ground for advancing care.”
The Stuart and Molly Sloan Precision Oncology Institute will help foster the research activities needed to make clinical breakthroughs in precision oncology. It’s also an example of how donor support provides catalytic funding for bold initiatives that push our scientific understanding further — and draw additional resources to bring scientific advances to patients.
“Fred Hutch is one of the world's truly special and unique biomedical institutions,” Lynch said. “The science that happens here is special.”
On April 1, 2022, Fred Hutchinson Cancer Research Center and Seattle Cancer Care Alliance became Fred Hutchinson Cancer Center, a single, independent, nonprofit organization that is also a clinically integrated part of UW Medicine and UW Medicine’s cancer program. Read more about the restructure.
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 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 email@example.com.
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