Fred Hutch Legacy Insiders

For Dina Lorraine, going on the GLP-1 drug Zepbound in April of 2025 was a no-brainer.

“I had no energy,” said the 58-year-old public relations professional from Auburn, Washington, who’s been treated for four separate cancers over the years. “I told my oncologist I couldn’t do normal activities like walking or gardening ― all of it was a struggle. Every time you do chemotherapy and take steroids, it adds weight. From breast cancer and this latest cancer, I’d gained 60 pounds.”

A year later, Lorraine has lost 70 pounds and is now doing a water-walking class. She’s got enough energy to keep up with her new grandbaby and is thinking about taking up tap dancing again, something she’s done since childhood.

“There are so many benefits, especially if you can figure out a level where you don’t have the gastrointestinal side effects,” she said of the weekly injectable drug, which works by mimicking human gut hormones that lower blood sugar, increase insulin secretion, and slow digestion so you feel full even without eating. “It gets rid of the hunger noise so you’re not constantly obsessing about the next thing you’re going to eat. I could have a plate of cookies in my house for a month and not touch them.”

The drugs’ side effects, though, have not been pleasant. Along with the occasional GI symptoms, Lorraine has lost hair and lean muscle mass and watched her “perky” reconstructed breasts disappear along with the unwanted pounds.

“I had a DIEP flap using stomach fat [to create new breasts] and they were great,” she said. “But they’re at my waist now, just skin bags. I have to go back in for revision surgery. It’s a trade-off.”

 

Four-time cancer survivor Dina Lorraine started on the GLP-1 drug Zepbound in April 2025 to help with her severe sleep apnea.
Photo courtesy of Dina Lorraine

A year later, Dina Lorraine has lost 70 pounds and her sleep and her sleep apnea have drastically improved. The four-time cancer survivor believes her weight loss will also help keep the four cancers she’s been treated for over the years from coming back.
Photo courtesy of Dina Lorraine

The new ‘miracle’ diet drugs

For decades, pharmaceutical companies and scientists alike have sought ways to help people lose weight, sometimes with disastrous results. Remember fen-phen, the “miracle” diet drug cocktail from the early ‘90s linked to fatal heart disease and billions in legal fees?

“There have been many, many efforts to develop weight loss drugs because there’s not a one-size-fits-all for weight loss,” said Fred Hutch Cancer Center’s Marian Neuhouser, PhD, RD, head of the Cancer Prevention Program. “So for many people, these new GLP-1 drugs are a game changer. They’re helping people with diabetes stay healthy and they’ve been extremely useful for millions of people who’ve not been successful using other ways to lose weight.”

Healthy weight loss has long been a north star for cancer prevention researchers like Neuhouser.

“Obesity is linked to about 13 different cancers,” she said. “And there are a number of cancers, including prostate cancer, postmenopausal breast cancer and colorectal cancer, where survivorship outcomes are not as good in people who have obesity.”

Much of the research done at Fred Hutch, Neuhouser said, is focused on getting cancer survivors to reduce their weight through diet and exercise “so they can have a better outcome.”

Can these new drugs help prevent cancer before it starts by tackling obesity and all the dysfunctional metabolic pathways that set the stage for cancer growth like chronic inflammation, excessive estrogen production, elevated leptin, insulin resistance, increased oxidative stress, etc.?

That’s one of the burning questions surrounding the new weight loss drugs. Along with this: Can GLP-1 receptor agonists, or molecular “on switches” like Ozempic and/or dual agonists like Zepbound (made from the synthetic peptide tirzepatide), reduce the risk of metastatic recurrence in cancer survivors?

Lorraine, who was diagnosed with thyroid cancer at 29, melanoma at 39, lobular breast cancer at 49 and peritoneal carcinoma a few years ago, believes the GLP-1 she’s taking won’t just help with weight loss, it will help keep those cancers at bay.

“I think it keeps away recurrence,” she said. “Fat creates estrogen [a common fuel for breast cancers] and stores it. Being not fat reduces my risk of recurrence.”

Neuhouser is more circumspect: “We don’t know the answers to any of those cancer prevention questions yet,” she said.

 

Fred Hutch’s Dr. Marian Neuhouser, head of the Cancer Prevention Program, speaks to U.S. Senator Patty Murray during a 2024 visit. “Obesity is linked to about 13 different cancers,” Neuhouser said. “And there are a number of cancers, including prostate cancer, postmenopausal breast cancer and colorectal cancer, where survivorship outcomes are not as good in people who have obesity.”
Photo by Robert Hood / Fred Hutch News Service

The great GLP-1 trade-off

But researchers across the country ― and the world ― are furiously conducting studies to determine if GLP-1s have cancer prevention potential.

Data presented at the 2026 ASCO Gastrointestinal Cancers Symposium showed GLP-1 users had a reduced risk of colorectal cancer. Other scientists are investigating whether GLP1-s can help with addiction, Alzheimer’s, anxiety, arthritis, cardiovascular disease, liver function, etc.

In the meantime, the new weight loss drugs do take off weight quickly and control Type 2 diabetes well, and the word is out. KFF research shows one in five adults in the U.S. has taken one form or another and 12% of adults ― that’s one in eight ― is currently on a GLP-1.

The only problem, as Lorraine mentioned, is the trade-off. And we’re not talking Ozempic face, Ozempic butt, Ozempic hands, Ozempic personality, Ozempic breath or the Ozempic shaming that happens when people stop using the drugs and regain weight.

“The biggest thing my oncologist was concerned about was my muscle loss,” she said. “He told me I’d lost a lot of lean muscle along with the fat and encouraged me to get some weights.”

Neuhouser stressed this happens no matter how the weight comes off.

“All weight loss is half lean, half adipose or fat,” she said. “It’s no different with GLP-1 receptor agonist drugs. But weight loss happens so fast with GLP-1 drugs that it may be more noticeable in a shorter amount of time.”

Lorraine boosted her protein intake to counteract this muscle loss, but Neuhouser said that alone may not be enough.

“Eating protein helps you maintain the muscle you have, but it doesn’t build it,” she said. “People think that if they take creatine supplements or some other protein, they’re going to build muscle, but that’s not correct. Exercise builds muscle.”

Neuhouser is concerned that prescriptions for GLP-1 drugs are not accompanied by referrals to registered dietitians.

“Most people are not given the ability to work with a registered dietitian who can help them create healthy eating patterns while on these drugs,” she said. “These drugs really decrease the appetite; some people struggle to actually eat, and some research suggests people may become malnourished because they don’t know what, when, or how much to eat because they’re not hungry.”

That’s exactly why Fred Hutch Director of Oncology Supportive Care and Screening Kerry McMillen, MS, RD, recommends patients using any kind of GLP-1 ask their oncologists for referrals to registered dietitians for guidance.

“It’s so important to have subject matter expertise along the oncology spectrum to guide appropriate recommendations,” she said. “Patients with questions about diet or concerns about losing muscle should ask their providers to recommend registered dietitians and/or physical therapists.”

But people don’t just lose muscle. Their wallets also take a hit. Most health insurance won’t cover them for weight loss, although they are often covered for diabetes, cardiovascular disease and obstructive sleep apnea, which is how Lorraine obtained her Zepbound prescription.

The high price ― which can range from around $150 to over $1,500 a month, per USA Today ― has created a barrier for many, but workarounds abound.

Prescriptions can be had via telehealth platforms like Ro and Hims/Hers, which have partnered with compounding pharmacies to create identical (or tweaked) GLP-1 formulations, though the U.S. Food and Drug Administration, or FDA, is currently looking at restricting this practice. In the meantime, manufacturers like Novo Nordisk, maker of the GLP-1 Wegovy (available as an injection or pill), and Eli Lilly, which makes both the injectable drug Zepbound and the new Foundayo GLP-1 pill, have also created discounted programs for employers and/or self-paying customers. Medicare, too, recently announced a GLP-1 Bridge program to help seniors access the drugs. And last week, Amazon One Medical jumped into the GLP-1 fray.

Not surprisingly, GLP-1s’ popularity has also led to a raft of cheap online knockoffs, with peptide companies skirting regulations by offering their untested, FDA-unapproved drugs “for research purposes only.” One emergency medicine blog reported people coming to the ER with profound hypoglycemia (low blood sugar) from using counterfeit pens filled with insulin rather than a GLP-1.

In a nutshell: buyer beware.

The last trade-off, of course, are the drugs’ infamous side effects. In addition to the well-documented nausea, vomiting, heartburn, bloating, constipation, diarrhea and muscle loss, more serious side effects ― think pancreatitis, gastrointestinal obstruction, thyroid tumors and vision issues ― have also been reported.

‘Stopping a GLP-1 is not only a medication transition, but a behavioral one. Patients may be dealing with the return of appetite, cravings, food preoccupation, discouragement, and fear of weight regain, often without much structured support. They’re on their own to figure this out and that lack of support is a major gap.’

― Fred Hutch psychologist and public health scientist Dr. Jonathan Bricker, holder of the Endowed Chair in Cancer Prevention

 

Fred Hutch breast cancer oncologist and medical director of the Adult Survivorship Program Dr. Vidhya Nair.
Photo by Robert Hood / Fred Hutch News Service

GLP-1s and cancer treatment

Even so, people are eager to get their hands on GLP-1s, including people dealing with cancer.

“Many of our breast patients ask about these drugs and whether it’s okay to use them during or after treatment,” said Vidhya Nair, DO, a medical oncologist and medical director of Fred Hutch’s Adult Survivorship Program. “Some patients are already on them, and we have to counsel that there may be compounded GI side effects when taken in combination with cancer treatment.”

Nair herself is hoping to conduct a study to see if a GLP-1 might help curb the side effects and improve adherence in breast cancer patients on endocrine therapy, a common breast cancer treatment that squelches the production of estrogen.

She cited studies presented at the 2025 San Antonio Breast Cancer Symposium showing patients on GLP-1s had reduced chemotherapy-related side effects, including reduced nausea and peripheral neuropathy. (Other findings released at SABCS showed GLP-1s increased side effects with endocrine therapy.)

“I thought that data was very interesting,” Nair said. “Most people are taking it for weight loss, and many patients are getting it online or from their PCP.”

Rick Grossman, 73, a retired Seattle entrepreneur and prostate cancer patient, was prescribed Zepbound by his cardiologist to improve his severe sleep apnea.

But like Lorraine, he believes the drug will do much more.

“There are like 12 reasons that I’m taking this,” he said. “I’ve been in remission for three years ― taking androgen deprivation therapy ― and during that time I’ve put on 20 or 30 pounds. That extra weight impacts blood pressure, cholesterol, sleep apnea, arthritis pain and other things, like my atrial fibrillation, my herniated esophagus and my fatigue.”

His main reason for taking the drug, though, is to prevent cancer recurrence.

“Research shows people with a higher BMI have a greater chance of cancer recurrence,” he said. “We don’t know whether dieting through Zepbound reduces that or not, but I think it’s worth trying even if it’s not proven. I’ve lost 10 to 12 pounds so far and it hasn’t been that hard.”

 

Fred Hutch’s Dr. Jonathan Bricker, shown asking a question at a faculty retreat, is working on ways to support people to maintain their weight loss without rebounding after they stop taking GLP-1s.
Fred Hutch file photo

Helping weight loss last

Unfortunately, research shows most people who go off the drugs gain their lost weight back; they also experience a sort of “metabolic whiplash” with a rebound of inflammation.

“There is no ‘GLP-1 offramp,’” said Fred Hutch psychologist Jonathan Bricker, PhD, holder of the Endowed Chair in Cancer Prevention. “Stopping a GLP-1 is not only a medication transition, but a behavioral one. Patients may be dealing with the return of appetite, cravings, food preoccupation, discouragement, and fear of weight regain, often without much structured support. They’re on their own to figure this out and that lack of support is a major gap.”

That’s why Bricker and his Health and Behavioral Innovations in Technology (HABIT) lab developed a telehealth behavioral intervention to work as a GLP-1 offramp.

“Between 50% and 80% of people who start taking GLP-1s stop by the end of the first year,” Bricker said. “We’re exploring why in a study. It’s also an opportunity to help people who are discontinuing this medication use ACT as a weight loss maintenance program.”

Like Neuhouser, Bricker stressed the importance of a behavioral change in weight loss.

“Behavioral interventions remain a core component of obesity treatment,” he said. “I think the ACT approach could be helpful since it helps people relate to cravings not as commands they must obey, but as experiences they can notice, acknowledge and let pass.”

Meanwhile, drug development and related research are exploding. Scientists at Stanford Medicine have found another molecule, BRP, that reduces appetite and body weight without the nausea, constipation, and muscle loss ― at least in mice and mini-pigs. Researchers at 23andMe just published data showing “a robust genetic association with GLP1 medication weight loss efficacy and associated side effects.” And a handful of new triple-agonist receptor drugs are currently in clinical trials.

What will the future hold? Hard to say, but cancer patients like Lorraine and Grossman are fine with the trade-offs for now.

“I recognize this is something brand new and that in five years, we may be saying we made a mistake in letting everybody use it,” Grossman said. “But for right now, it’s helping me.”

Toshio “Toshi” Tsukiyama, PhD, DVM, professor and associate director of the Basic Sciences Division at Fred Hutch Cancer Center, has received the inaugural David and Deborah Lycette Endowed Chair for Cancer Research.

The new endowed chair, established by a couple who have been involved with Fred Hutch since its earliest days, will advance precision oncology by supporting Tsukiyama’s research into how cells package, store and use genetic material.

With a gift to endow a faculty chair, visionary donors empower scientists to pursue transformative ideas. Generous supporters have endowed 55 chairs at Fred Hutch to date, honoring faculty members and giving them flexible funding for innovative research. Endowment gifts are critical to long-term sustainability and a cornerstone of the Campaign for Fred Hutch, which is bringing the community together to increase the pace and scale of discovery.

“Dr. Tsukiyama is changing the way we think about fundamental aspects of biology,” said Fred Hutch President and Director Thomas J. Lynch Jr., MD, holder of the Raisbeck Endowed Chair. “He is cracking the code that controls how cells turn genes on and off, which is essential for knowing what goes wrong in cancer and what to do about it.”

“Receiving this endowed chair is a game changer for my lab — it will help with every aspect of our research,” said Tsukiyama, who trained as a veterinarian in Japan before discovering a passion for microbiology. He went on to earn a PhD before coming to the U.S. for a postdoctoral fellowship at the National Institutes of Health in Bethesda, Maryland.

The power of sleeping cells

Since joining Fred Hutch in 1997, Tsukiyama has focused on chromatin, the molecular scaffolding that makes it possible for a seven-foot strand of DNA to precisely tuck, fold and wrap itself into a microscopic bundle that fits into the nucleus of a cell. Chromatin arranges DNA to make genes accessible when they’re needed. And it plays a critical role in cell division, ensuring DNA is divvied up correctly in the new daughter cells. 

Tsukiyama’s research has revealed that chromatin is also vitally important when cells are not dividing but are in a dormant phase, called quiescence. 

“For a long time, researchers weren’t interested in quiescent cells because they didn’t seem to be doing anything,” said Tsukiyama. “But it turns out that these sleeping cells are important, both for normal life and for cancer biology. For me, this field has been a research gold mine.”

For example, quiescence may explain how some cancers evade drugs, recur and spread. Because many drugs target rapidly dividing cells, cancer cells can avoid detection by going to sleep — and they can stay asleep for months or years before becoming active again. Quiescent cells may also move stealthily from one part of the body to another, helping cancer spread.

“If we can find a way to detect these cells and wake them up artificially, we can make them more sensitive to drugs,” Tsukiyama said. “But we don’t know how to do that yet. First, we need to understand how cells stay dormant for that long and what’s special about them during quiescence that we can change to make them more active.”

This knowledge, which can only be gained through fundamental research, will lay the groundwork for better therapies.

His lab’s focus on sleeping cells, he said, started “in the most Fred Hutch way imaginable” — a hallway conversation with a colleague. That’s where geneticist Linda Breeden, PhD, who is now retired, floated the idea of leveraging Tsukiyama’s molecular biology expertise to deepen her genetics-focused research on cell dormancy. Their collaboration started in 2012 with a pilot project. But soon “it got so interesting that now the entire lab studies different aspects of dormancy,” Tsukiyama said. 

As technologies have become more sophisticated, so have the questions his team can ask and answer about the underlying processes triggered by chromatin remodeling, the shape-shifting maneuvers that make DNA available for whatever purpose it’s needed — whether that is to transcribe proteins, replicate, go to sleep or wake up.

Not long ago, the nuclei of the yeast cells Tsukiyama studies looked like fuzzy dots through his microscope. By contrast, today’s super-resolution microscopy is so sharp, he can see the texture of DNA inside the nucleus. “This was something we could only dream about just a few years ago,” he said. Soon, he predicts, scientists will be able to watch genetic changes in live cells in real time. 

Linking their legacy to a trusted organization

Tsukiyama’s research is precisely the type of fundamental discovery David and Deborah Lycette aim to advance — with the ultimate goal of preventing and treating cancer.

The couple, who are retired attorneys, have been involved with Fred Hutch since it was a mere idea. David Lycette joined the Board of Trustees at its very first meeting in January 1972 and served on the board for more than 30 years.

In the early days, the Lycettes hosted dinners at Fred Hutch’s original location to introduce the fledgling center to local business and civic leaders, and lab tours with scientists were the highlight. 

“It was marvelous to hear researchers talk about what they were doing and why it was important,” Deborah Lycette said. It still is, she added.

While the Lycettes have stepped back from day-to-day involvement at Fred Hutch, they are avid supporters. When they learned about the Anniversary Challenge — and the goal of matching gifts of $1 million to create 25 new endowed chairs in six areas of scientific focus — they jumped at the opportunity to link their legacy with the organization they have trusted for so long.

“We hope Toshi’s research will result in new information about cancer causes and treatments,” David Lycette said. “Along the line, we know some things you look into won’t work, and that’s important, too.” 

Optimism and technology drive progress

As a scientist, Tsukiyama can guarantee that some things won’t work out. “Most principal investigators are unbelievably optimistic,” he said. “We have to be, because 90% of what we do is troubleshooting — an experiment doesn’t work, or equipment fails, or a grant doesn’t get funded. These things happen all the time.”

His innate optimism helps him reframe these setbacks as building blocks for new ideas.

“There are so many questions to be answered,” Tsukiyama said, and the endowed chair will enable him to follow where the science leads.

Immunotherapy has joined surgery, radiation and chemotherapy as one of the major pillars of cancer treatment, one that sometimes results in lifelong protection against a cancer ever coming back.

This approach — which coaxes the body’s immune system into “seeing” cloaked cancer cells again — includes cellular immunotherapies like CAR T cells, immune checkpoint inhibitors and antibody-drug conjugates, therapies that have worked remarkably well for a small group of patients, with response rates of 37% in melanoma and higher in select colorectal cancers.

But for most patients — including many diagnosed with these “responsive” cancers, as well as those with pancreatic, uterine or germ cell tumors — immunotherapy has not made a difference.

“While melanoma or MSI-high colorectal patients [that is, patients with tumors with high levels of microsatellite instability] have the best chance of responding to these treatments, a large proportion of patients even in these responsive indications don’t benefit,” said Fred Hutch Cancer Center’s Kevin Barry, PhD, a molecular biologist whose lab focuses on the workings of the immune system.

“Our immune system protects against cancer, and the new immunotherapies work by re-activating the immune system to kill cancer and, in some cases, essentially cure patients,” he said. “But the immune system can be overrun by cancer. Only around 30% of patients respond to this type of treatment. Even in melanoma where we see the most promise of these drugs, we have work to do.”

Barry will soon launch into that work thanks to a $270,000, two-year grant from the American Cancer Society. With it, he’ll investigate new ways to boost immunotherapy responses in metastatic (or advanced) melanoma patients by exploring how the tumor microenvironment helps cancer cells evade our innate immune system.

“We plan to study and define the mechanisms that control the innate immune system within the tumor and how they are harnessed by cancer to block protective immune responses,” he said.

His goal? To identify novel pathways that regulate these protective immune responses to cancer that can then be exploited via new therapies that coax the immune system back into destroying cancer cells, improving patient responses and prolonging patient lives.

How the immune system fights cancer

The innate immune system ― which each of us is born with ― is the first line of defense against infection and disease, including cancer.

“The innate immune system has two major roles,” Barry said. “The first is to initiate disease control and the second is to activate and shape the sterilizing immune response, that is, the immune response that kills cancer.”

Innate immunity, he said, lays the foundation for protective immune responses; innate immunity has also been shown to control patient survival and responses to current FDA-approved immunotherapies.

“Together, these findings make the innate immune system an exciting target for new immunotherapies,” Barry said. “Our aim is to define the mechanisms that control innate immune responses to melanoma.”

Dendritic cells, part of the immune system, often look “hairy,” thanks to their long spikes or dendrites, functional projections the cells use for immune surveillance.
Stock photo from Getty Images

Cancer avoids detection through a process called tumor immune evasion, hijacking the body’s mechanisms that exist to protect it from attacking its own healthy cells.

“In order to develop immunotherapies that fully harness the power of the immune system to fight cancer, it’s imperative to understand how tumors evade the immune system,” Barry said.

Examples of tumor immune evasion include immune cell exclusion, reduced recruitment of immune cells to the tumor, the production of immunosuppressive cytokines and tumor cell down-regulation of neoantigen expression, he said.

With the ACS grant, Barry and his team will focus on a novel form of tumor immune evasion that blocks protective immune responses through the activity of a specific innate immune cell in the tumor, the type 2 conventional dendritic cells, or cDC2.

Conventional dendritic cells, or cDCs, are specialized immune cells found in tissues that are exposed to the environment ― think skin, lungs and gut mucosa. There, they act as sentinels, capturing antigens like viruses, bacteria or cancer cells and presenting them to T cells to initiate the adaptive immune response. As the main antigen presenting cells, cDCs basically act as a bridge between the innate and the adaptive immune system. Through them, the body learns to recognize, destroy, and “remember,” or adapt, to specific pathogens or bacteria.

This category of dendritic cells have two types, cDC1s and cDC2s, but only cDC1s have been studied adequately, “due to their ability to efficiently induce CD8 T cells and their ability to be manipulated genetically,” Barry wrote in his proposal, adding that “tumor-induced cDC1 dysfunction is a form of immune evasion, resulting in reduced anti-tumor CD8 T-cell responses and reduced protection from cancer.”

But cDC2 dysfunction in the tumor is less well-defined, he said. Ditto for its role when it comes to shaping anti-tumor CD8 T-cell responses.

Barry’s research will attempt to fully investigate how innate immune dendritic cells shape adaptive immune responses. Specific aims are to develop models to test the effects of cDC2 priming on T-cell function in vivo (in living preclinical models) and determine how the phenotypes and spatial organization of cDCs shape CD8 T-cell responses in human metastatic melanoma.

“These studies will provide a novel understanding of the regulation of CD8 T-cell responses in cancer and will allow us to begin to develop treatments to disrupt the tolerogenic, or immune tolerant, role of cDC2s in cancer,” he said.

“A significant output of our studies will be the future development of novel immunotherapies that work in concert with existing treatments to enhance survival of patients with primary and metastatic cancers.”

Why study this in melanoma?

Barry chose to conduct research on melanoma ― the most dangerous form of skin cancer ― because it was one of the first cancers on which immunotherapy was used.

“Melanoma has the longest history with immunotherapy,” Barry said. “But we believe that what we learn from studying dendritic cells in melanoma will translate to other solid tumors, as well.”

Earlier research, he said, suggests the pathways found in melanoma hold true across other types of cancers.

“We don’t know if it will be true for all solid tumors,” he said. “But it will be true for at least some other solid tumor indications.”

Barry is one of three Fred Hutch researchers to receive 2026 awards from the American Cancer Society. Other awardees include epidemiologist Trang VoPham, PhD, MPH, MS, and clinical researcher and oncologist Kate Markey, MBBS, PhD.

The American Cancer Society’s mission is to improve the lives of people with cancer and their families through advocacy, research and patient support, to ensure everyone has an opportunity to prevent, detect, treat and survive cancer.

Rare cancer expert Taran Gujral, PhD, cares more about what a cancer drug can do than what it is designed to do.

His lab at Fred Hutch Cancer Center investigates a promising target for cancer drugs — enzymes called kinases, which send signals regulating almost every activity in a healthy cell’s life cycle including growth, division and the controlled death of damaged cells.

“In cancer, many of these kinases become overactivated in different ways,” Gujral said. “They can be switched on by mutation, by fusing with other genes, or simply by being produced in higher amount, which is why they’re such important target for cancer treatment.”

A class of drugs that blocks the molecular activity of malfunctioning kinases — called kinase inhibitors — grew from a single drug in early 2000s to 100 kinase inhibitors by the end of 2025, each designed for one specific kinase and most aimed at treating cancer.

In one of the most comprehensive studies to date, published this week in the journal Nature Biotechnology, Gujral and his team show that many FDA-approved drugs can block more than the single kinase they were designed to target, including many cancer-causing mutations.

For example, Gujral and his colleagues found that kinase inhibitors designed for mutated forms of lung cancer also work on specific types of brain and pancreatic cancer. A drug designed to treat leukemia can also help a drug designed for lung cancer work better.

The study expands the number of kinases that can be inhibited by an FDA-approved drug from 89 to 235, with relevance across many kinds of cancer.

Gujral’s lab in the Human Biology Division at Fred Hutch also developed a free, public interactive web-based tool called Kinase Inhibitor Repurposing Hub (KIRhub) to visualize that data, which maps new avenues for research, precision medicine, and potential therapies for challenging cancers that lack effective treatment options.

Drugs that block the on-switches for cancer-fueling processes

Kinases make things happen in the cell by precisely regulating the activation of specific proteins — the cell’s molecular workers — which enables them to initiate signaling pathways for a wide variety of cellular processes essential to life.

To do this, a kinase must first grab an energy-storing molecule called ATP, which contains three chemical groups called phosphates that function like a kind of battery.

The kinase tucks ATP into a binding pocket between its two halves. It then removes one of ATP’s phosphates and attaches it to the adjacent protein that the kinase is made to activate.

The transferred phosphate “battery” carries the extra energy needed to change the protein’s function and initiate cellular signaling.

Kinase inhibitors are small‑molecule drugs that prevent this battery transfer by nestling into the pocket where ATP normally fits, blocking ATP from binding.

“If they occupy the ATP-binding pocket so the ATP cannot bind anymore, then there’s no phosphate to be transferred and the whole signal stops,” Gujral said.