Kuni Foundation awards $7M to drive adult oncology research forward

Eight researchers specializing in adult oncology with Fred Hutch Cancer Center and the University of Washington have been awarded a total of $7,268,202 from the Kuni Foundation’s Discovery Grant program to support early-stage research in developing promising new treatments. 

At a time when research funding has become significantly harder to secure, the Kuni Foundation has reaffirmed its commitment to provide funding for high-risk, high-reward cancer research projects that could lead to innovative therapies for rare, underfunded or difficult-to-treat diseases.

This year, due in part to slashed National Institutes of Health (NIH) research funding, applications for Kuni Foundation grants increased 300% from last year.

Based in Vancouver, Washington, the Kuni Foundation provides grants to support Pacific Northwest-based cancer researchers looking to identify new approaches to cancer treatment or to bring new advances to clinical care. Discovery Grants, with a maximum value of $1,050,000, support a specific research project for up to three years.

“The Kuni Foundation is deeply committed to advancing cancer research in the Pacific Northwest, recognizing that bold investments in science and innovation are essential to unlocking lifesaving breakthroughs,” said Angela Hult, Kuni Foundation president. “We’re honored to support this vital work powered by the exceptional people at Fred Hutch Cancer Center. Now more than ever, sustained funding for scientific research is critical — to accelerate progress, empower visionary scientists and bring hope to individuals and families affected by cancer."

Discovering treatment options for locally recurrent breast cancer

Meghan Flanagan, MD, MPH, a Fred Hutch surgical oncologist and assistant professor of surgery at the University of Washington School of Medicine, found that limited treatment options existed for patients whose hormone-positive breast cancer recurred after their initial treatment. These were recurrences localized in breast or axillary tissue, meaning they had not metastasized (that is, spread) to other parts of the body. 

The risks are potentially serious: nearly 25% of patients with isolated non-metastatic locoregional recurrences of breast cancer tumors (ILRR), eventually develop incurable metastases.

Around 70% of breast cancers are hormone positive, meaning they have estrogen receptors on the cell membranes, as well as HER-2 negative, that is, they contain no receptors for a growth factor known as HER-2.  ER+/HER-2 negative cancers are often treated with hormone-blocking drugs, but a recurrence after treatment could indicate resistance to current drugs.

While only 5-10% of breast cancer patients experience a local or regional recurrence, this translates to thousands of patients annually in the U.S. who need treatment to keep the recurrent tumor from metastasizing.

Looking for data on the best practices for treating ILRR, Flanagan realized that no central database existed to help physicians determine the best course of treatment for these patients. So, she created one herself.

“There are no databases that are available nationally that capture cancer recurrence,” Flanagan explained. “That’s why it’s such an understudied patient population.”

Flanagan’s three-year, $368,202 Discovery Grant (her second from the Kuni Foundation) will fund the development of a database to capture information on ILRR and how patients who experience eventual metastasis are treated. The tumors themselves will then be subjected to whole exome sequencing, a process that analyzes the protein-coding regions of a patient’s genome, with the goal of understanding resistance mechanisms and developing more targeted treatment protocols.

Flanagan credits her own patients with local recurrences for inspiring the project. She sees patients at Fred Hutch’s South Lake Union Clinic and UW Medical Center – Northwest. 

“Many of my research questions come from seeing patients,” Flanagan said. “In this study, our hope is that our findings will inform the design of clinical trials targeting ILRR that could fundamentally shift the treatment paradigm for this disease.”

Enhancing immune function in pancreatic cancer

Pancreatic cancer tumors are exceptionally skilled at suppressing the body’s immune cells.

Pancreatic ductal adenocarcinoma (PDAC) is particularly lethal, with a five-year survival rate of only 4.6%. Taran Gujral, PhD, an associate professor in Fred Hutch’s Human Biology Division, hopes to demonstrate the promise of a new drug target for PDAC with his three-year, $1,050,000 grant from the Kuni Foundation.

Gujral, an expert on cell signaling, will examine why the outer membrane of cells with PDAC express a receptor called “Frizzled,” normally expressed only in cells during fetal development. The “Frizzled” receptors are genetically similar to a family of receptors in fruit flies; a fly without the “Frizzled” gene will have wings with a frizzy or distorted appearance.

These receptors are associated with a cell signaling process known as wnt (pronounced “wint”) signal transduction, which controls many fundamental aspects of cellular function. A protein ligand binds to “Frizzled,” instructing the cell to grow, divide or migrate. In fetal development, this is a welcome occurrence. In cancer, it can prove deadly.

Gujral’s lab will use mouse models that express genes linked to PDAC to test whether a new kind of antibody that targets the “Frizzled” receptor can block tumor growth and spread. 

Prior work in Gujral’s lab demonstrated that the new antibody could both bind to “Frizzled” and strengthen the action of the body’s effector T cells. The new study aims to understand both the mechanism by which “Frizzled” expression occurs in PDAC cells, and to determine whether the antibody can shrink tumors and strengthen the immune response in mouse models.

Fred Hutch immunologist Philip Greenberg, MD, head of the Program in Immunology and holder of the Rona Jaffe Foundation Endowed Chair, will collaborate with Gujral to carry out the study. 

Gujral stressed the importance of early-stage research support from the Kuni Foundation in helping his team to acquire the data necessary for later-stage funding from the NIH.

“Foundations like the Kuni Foundation are really helpful for scientists to help bridge the period where we can collect proof-of-concept data to eventually earn long-term funding to sustain the project,” Gujral said.

Gujral previously received a Kuni Foundation grant of $75,000 to develop an AI-based drug screening platform that can match patient tumors with available drugs. 

Searching for new approaches in a rare form of pediatric leukemia

A type of pediatric leukemia caused by a phenomenon known as gene rearrangement has earned John Colgan, MD, a new assistant professor in the Clinical Research Division at Fred Hutch, his first research grant as a principal investigator in the U.S.

A native of Sydney, Australia, Colgan joined Fred Hutch in May after completing a one-year fellowship in a bone marrow transplantation and immunotherapy at Seattle Children’s.

He will use his three-year, $900,000 Kuni Foundation grant to study potential new therapies for KMT2A-rearranged (“KMT2A-r”) leukemia, a type of leukemia that occurs in around 15-20% of pediatric patients. Specifically, Colgan will examine the genetic profile of KMT2A-r leukemic cells that are resistant to a drug that targets menin, a molecule that binds to the KMT2a protein that causes it to overwork in leukemia cells. 

Resistance to the menin-inhibiting drug, revumenib, has been observed in 40% of patients with KMT2A-r leukemia. Colgan aims to analyze the genetic profile of revumenib-resistant KMT2A-r leukemia and to search for targeted combinations of therapies that could be used to treat this difficult type of cancer, including targets on cancer cells known as “neoantigens” (or “new antigens,” so named because the target only appears on cancer cells). 

“We believe this project has the potential to make a significant contribution to both the survival and quality of life of children with KMT2A-rearranged leukemia,” Colgan said.

Colgan’s collaborators include pediatric oncologist Marie Bleakley, MD, PhD, a professor in Fred Hutch’s Translational Science and Therapeutics Division who holds the Gerdin Family Endowed Chair, and Scott Furlan, MD, an assistant professor in both the Translational Sciences and Therapeutics and Public Health Sciences divisions at Fred Hutch. The collaboration extends internationally as well, with critical preclinical mouse models for the project developed in Australia.

“Pediatric cancer is such an underresourced and underfunded area,” Colgan said. “We’re very excited that the Kuni Foundation chose to fund our work. This disease affects a very important part of the population and at the end of the day, this project could improve not only patient outcomes, but also their quality of life. These grants make a large difference in helping us as young investigators as we start our research careers.”

New drug candidates to target cell cycle proteins in HPV-negative squamous cell carcinoma

Executive Vice President and Chief Scientific Officer & Deputy Director Bruce Clurman, MD, PhD, will use a three-year $1,050,000 Kuni Foundation grant to develop a multi-lab approach to search for better therapies for HPV-negative head and neck squamous cell carcinoma (HNSCC), a type of head and neck cancer that is particularly resistant to treatment. Clurman holds the Rosput Reynolds Endowed Chair.

Squamous cells — which are flat, with an appearance that resembles fish scales — are found in the thin tissues that form the surface of skin and the lining of various parts of the body. HNSCCs are a group of cancers that arise from squamous cells lining the mouth, tongue and throat caused by the human papilloma virus (HPV) or by environmental exposures such as smoking.

HPV-positive HNSCC, associated with the virus, can have relatively good prognosis. However, HPV-negative HNSCC, caused by genetic mutations that arise from environmental toxins, is often more difficult to treat and outcomes have not progressed in several decades.

Clurman will build on previous research demonstrating that two specific proteins involved in regulating how cells divide, Wee1 and CDK4/6, can be targeted in HNSCC with drugs known as inhibitors. (CDK stands for cyclin-dependent kinase; the CDK family of proteins, delineated by numbers, activate other proteins in the cell cycle pathway through a process known as phosphorylation. CDKs are “dependent” on another protein in the cyclin family, which activates CDK by binding to it.)

The project is highly collaborative, with eight team members at Fred Hutch and UW Medicine, two of whom are Kuni Foundation grant recipients themselves: Gujral and Brittany Barber, MD, a Fred Hutch surgeon and assistant professor of otolaryngology head and neck surgery at UW School of Medicine, who received a $75,000 Kuni Foundation grant in 2021 to study tongue cancer in otherwise healthy young people.

“With this grant, we’re not just trying to understand new mechanisms of how the disease develops, we’re also looking to find new ways to treat it based on understanding those mechanisms,” Clurman said. “A lot of drugs have shown promise. We want to figure out how to use them effectively, both by understanding the mechanisms of what they do, and by putting them through a drug-screening process developed at Fred Hutch that identifies promising drug candidates based on patient tumor characteristics.”

Speeding up the delivery of radiation therapy to enhance patient outcomes 

Jing Zeng, MD, vice chair of Clinical Affairs in the Department of Radiation Oncology at the UW School of Medicine and a professor in the Radiation Oncology Division at Fred Hutch, is pioneering a form of radiation therapy for solid tumors known as FLASH radiation.

She will use her three-year, $1,050,000 Kuni Foundation grant to complete preclinical research in mouse models and to design and launch a Phase 2 clinical trial focused on patients with lung and liver cancers.

Radiation as a form of treatment for solid tumors has been around since X-rays were first used to treat cancer over a century ago. However, radiation treatments can cause significant side effects, as the high-energy electromagnetic waves begin to dissipate as soon as the waves hit human tissue. While the target tumor still receives a radioactive dose that can help mutate tumor DNA so that it can no longer divide, radiation therapy can also induce unwanted changes in healthy tissue. 

Proton therapy uses positively-charged particles found in the nucleus of atoms to deliver radiation with far fewer side effects than traditional radiation therapy. FLASH radiation is proton therapy with a twist: it is delivered 1,000 times faster than current proton therapy protocols. 

“Technology has improved to the point where we know exactly how to change the speed at which we deliver radiation, as well as the amount of energy harnessed in the beam,” Zeng explained. “These variables determine how far the beam of radiation travels before it stops. FLASH therapy delivers radiation much faster than existing proton therapy, and we’ve shown in mouse models that it leads to far fewer side effects.”

Zeng has previously received research support from the Kuni Foundation, including an Imagination Grant in 2020 and a Discovery Grant in 2021. Her current project builds upon findings from her earlier Kuni Foundation-funded research.

“Our initial Kuni grant in 2020 helped us launch our research program into this ultra-high-dose-rate radiation protocol,” Zeng said. 

Enabling the brain’s natural immune system to fight cancer before it starts

Stopping metastasis, where cells detach from their original location, lodge into other organs, and begin to divide, is a critical goal in cancer treatment. Metastasis to the brain is particularly difficult to treat, with mortality rates nearing 100% and life expectancy measured in months.

Fred Hutch's Cyrus Ghajar, PhD, who holds the Peter S. Lefkarites Memorial Endowed Chair and is director of the Center for Metastasis Research eXcellence (MET-X), will use a three-year, $1,050,000 grant from the Kuni Foundation to examine whether a type of brain cell known as microglia could be activated to seek out and destroy cancer cells in the brain before they develop into metastases.

His collaborators include Evan Newell, PhD, a professor in the Vaccine and Infectious Disease Division; Aakanksha Singhvi, PhD, an associate professor in the Basic Sciences Division; and Sara Hurvitz, MD, the head of hematology and oncology at Fred Hutch and UW who holds the Smith Family Endowed Chair in Women’s Health.

Because of the blood-brain barrier, disease-fighting T cells do not travel to the brain as often as they do to other organs to seek out and destroy cancer cells.

In the brain, this immune-system function is performed by microglia.

In a prior experiment, Ghajar’s team observed live mouse brains with dormant cancer cells in a process known as intravital imaging. They thought astrocytes, which normally deposit proteins that can drive cells into a dormant state, were keeping the cancer cells at bay. By pointing the intravital imaging laser at the astrocytes, they thought the cells would die and the neighboring cancer cells would start multiplying.

“But that’s not what happened,” Ghajar explained.

Instead, the cancer cells themselves died. They concluded that the astrocytes themselves were preventing microglia from attacking the dormant cancer cells. Ghajar’s project will aim to uncover the mechanism by which astrocytes appear to keep the microglia from performing their natural role in the brain’s innate immune system.

“This could be a totally new way of unleashing the immune system in the brain to eliminate these dormant cancer cells,” Ghajar said. “If we’re successful, we’ll have cancer survivors who don’t have to worry about brain metastases anymore.”

This is Ghajar’s first grant funded by the Kuni Foundation. He noted that in a challenging environment for the life sciences, support from private foundations is critical to keep lifesaving research going.

“It’s enabling science to happen that otherwise wouldn’t be able to happen,” he said.

Preventing epithelial cancer cells from transforming into new cell types

Epithelial cancers affect the cells found in the body’s protective membranes, such as the outer layer of skin, and the lining cells of breast ducts and lobules, as well as the airways of the lungs.

In advanced cancers, these cells have shown the ability to hide from treatments by literally turning into other cell types, a phenomenon known as lineage plasticity. It is a key feature of embryonic development, but in cancer, it can drive both metastasis and drug resistance. 

Cancer cell biologist James Alvarez, PhD, an associate professor in the Public Health Sciences and Human Biology divisions, will use his three-year, $750,000 Kuni Foundation grant to fund a study to help develop new drugs that prevent lineage plasticity, as well as therapies to treat tumors that have undergone the process of transdifferentiation, where the cells have already changed from one type to another. 

Alvarez will collaborate with fellow Fred Hutch scientists Gujral and Peter Nelson, MD, vice president of Precision Oncology and director of the Stuart and Molly Precision Oncology Institute at Fred Hutch. Nelson holds the Stuart and Molly Sloan Precision Oncology Institute Endowed Chair.

Alvarez’s team will utilize a machine-learning tool developed in Gujral’s lab to identify small molecules known as kinase inhibitors that can prevent lineage plasticity. The study will also examine whether a cancer drug, palbociclib, might be effective against lung and prostate tumors in mouse models.

Alvarez’s lab previously found that palbociclib could prevent transdifferentiated lung cancer cells from growing in culture. Nelson will provide expertise on lineage plasticity as well as consultation for developing ways to translate the project’s findings to a clinical setting.

The study’s ultimate goal is to determine whether lineage plasticity in cancer cells is driven by a common mechanism. A discovery of that magnitude would lay the foundation for developing drugs that can arrest lineage plasticity in many types of cancer where cells undergo transdifferentiation.

“Kuni Foundation funding will be instrumental in performing these experiments,” Alvarez said. “This is an intensive, collaborative effort that requires deep resources. The Kuni Foundation has provided us with a transformational grant that allows us to generate the data we need to apply for further NIH funding to support future work in this area.”

Enriching tumor-fighting T cells in renal cell carcinoma

Renal cell carcinoma (RCC) is the most common kidney cancer found in adults. Metastatic RCC is essentially incurable, with over 14,000 deaths in the U.S. every year.

Oncologist and cancer immunologist Edus Houston (Hootie) Warren, MD, PhD, a professor in the Translational Science and Therapeutics Division, will use his three-year, $1,050,000 Kuni Foundation grant to determine whether a particular type of T cell that can specifically recognize and attack RCC tumors can be identified in patient tumors, and then expanded in a laboratory setting while retaining its disease-fighting characteristics.

He will collaborate with Scott Tykodi, MD, PhD, an associate professor in both the Fred Hutch Clinical Research Division and the Division of Hematology and Oncology at the UW School of Medicine.

Solid tumors can outflank the immune system by suppressing the body’s ability to get enough effective T cells into the area where tumor cells are located. Warren hopes to develop a new treatment approach for kidney cancer known as tumor-infiltrating lymphocyte (TIL) therapy, which was approved by the FDA in 2024 for advanced melanoma but has not yet been used in kidney cancer.

The project aims to identify specific cell markers on T cells in kidney tumors that are most likely to fight the tumors effectively (called “tumor-reactive” T cells), and to optimize techniques for expanding these T cells in the lab. Warren’s group will test the expanded tumor-reactive cells to determine how effective they are at killing RCC tumor cells taken from patient samples.

RCC is a deeply underfunded disease. Recently, all funding for the Congressionally Directed Kidney Cancer Research Program was slashed, making Kuni Foundation support critical for this investigation.

“The high-risk, high-reward question in our research is our hypothesis that there are unique target antigens on kidney cancer cells encoded by portions of the genome we do not fully understand yet,” Warren said. “We also believe T cells that recognize these targets exist and retain the ability to divide, multiply, and kill tumor cells. But our hypothesis is not yet supported by sufficient data to qualify for an NIH-level grant, making the Kuni Foundation’s support a critical part of this work.”