Sita Kugel, PhD, pancreatic cancer researcher and a professor at Fred Hutch Cancer Center, is determined to translate her research into new tailored treatments for patients with pancreatic cancer. Kugel, the inaugural recipient of the Leung Roy Family Endowed Chair, investigates the molecular drivers of cancer and looks for ways to target them with small molecules and immunotherapies.
After decades of hard work by researchers and frustratingly few advances for patients, new treatment options for metastatic pancreatic cancer may be just around the corner.
As excitement in the field builds, Kugel is preparing to launch a clinical trial later this year based on discoveries made in her lab — in partnership with medical oncologist Rachael Safyan, MD. Safyan is director of the Clinical Research GI Oncology Program and an assistant professor at Fred Hutch and UW Medicine.
Yin Ling Leung, a patient of Safyan, benefited from the years of incremental progress by researchers that made the recent breakthroughs possible. Now, she and her husband, Shaibal Roy, have established this endowed chair to accelerate the pace of urgently needed pancreatic cancer research and change the outcome for other families in the same situation.
“By supporting the research happening in the Kugel Lab, I get to touch the future,” Leung said. “It’s a future that I may or may not be around to see, but I’m hoping that the world will be a better place for patients because of this work.”
The majority of patients with pancreatic cancer are diagnosed at an advanced stage, since symptoms may not be noticeable or specific until the disease has progressed. Pancreatic cancer is typically treated with chemotherapy and, when possible, surgery, but metastatic disease can become treatment-resistant within months.
While immunotherapies have transformed treatment for some cancers, pancreatic tumors are notoriously difficult to treat. Their dense structure can prevent both drugs and immune cells from reaching cancer cells, and most pancreatic cancers are driven by a mutated version of the KRAS gene, which researchers have spent decades trying to target effectively.
Recent developments are finally showing that it's possible. Clinical trials of a KRAS inhibitor have extended the lives of many patients, including Leung.
Since starting her lab at Fred Hutch in 2017, Kugel has focused on pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer. In looking for differences between the two major subtypes of PDAC, classical and basal, she discovered an unexpected vulnerability in this hard-to-treat cancer’s defenses.
What is precision oncology?
Hear from Sita Kugel, PhD, and Rachael Safyan, MD, about the promise of precision oncology for pancreatic and other cancers in this video.
Kugel’s team found that the more aggressive basal subtype is particularly sensitive to a class of drugs that inhibits cyclin-dependent kinases (CDKs), proteins that help regulate cell growth and become overactive in many cancers. This finding could be the basis for the first precision oncology approach for the basal subtype.
To translate this discovery into progress for patients, Kugel has teamed up with Safyan to design a Phase 1b clinical trial that makes use of a special “window of opportunity.” Before their scheduled surgery, newly diagnosed patients enrolled in the trial will receive a two-week course of the novel therapy.
While this short duration of treatment may not be enough to influence outcomes in this trial, Kugel’s team will learn all they can from samples donated by patients to inform their next steps.
Kugel and Safyan are already planning the next iteration of the trial that would offer the targeted treatment, in combination with standard chemotherapy, to patients with metastatic disease.
“As a clinical investigator, I can't imagine a better research partner,” Safyan said. “Sita is endlessly curious and relentlessly focused on moving discoveries from the bench to the bedside, where they can help patients.”
Distinguishing the basal subtype of PDAC from the classical subtype requires advanced sequencing techniques that are costly and time-consuming. Yet identifying a patient’s subtype could help guide treatment decisions and clinical trial enrollment.
The challenge is that the subtypes differ by patterns of gene expression, so under a microscope they look very similar. The Kugel Lab discovered two biomarkers that make the distinction visible when paired with fluorescent dyes: tumor samples glow green for classical and red for basal.
These findings may also point to new treatment strategies. One biomarker, the protein HMGA2, appears to drive the basal subtype’s aggressive growth and chemotherapy resistance, making it a potential therapeutic target. Kugel and her team are now refining the diagnostic approach while exploring ways to target tumors with high levels of HMGA2, including combinations of immunotherapies and the KRAS inhibitor that is receiving national attention.
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Philanthropic support has long been a launchpad for Kugel’s translational research, helping her gather the necessary preclinical evidence and prepare to launch the upcoming clinical trial.
With a gift to endow a faculty chair, visionary donors like the Leung Roy family empower scientists to pursue transformative ideas. Generous supporters have endowed more than 60 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 together our community to radically increase the pace and scale of discovery.
“Dr. Kugel is energizing a field that urgently needs real progress for patients,” said Fred Hutch President and Director Thomas J. Lynch Jr., MD, who holds the Raisbeck Endowed Chair. “Moving discoveries like these from the bench to the bedside is at the heart of what we do at Fred Hutch.”
With the annual funds provided by the Leung Roy Family Endowed Chair, Kugel will have the freedom to pursue the early-stage ideas that don’t yet qualify for grant support.
“You need to do the experiment before you can secure the grant,” Kugel said. “Having seed funding for high-risk, high-reward projects allows me to explore innovative ideas that have the potential to transform patient care.”
Her ideas include novel ways to detect pancreatic cancer at its earliest stages using biomarkers, something that is particularly meaningful to the Leung Roy family.
Leung and Roy are cofounders of Cozeva, a health care technology company. “On a population health level, we want people to get the right screenings to catch cancer at earlier stages,” Leung said. “It’s interesting that pancreatic cancer does not have good screenings.”
Leung was diagnosed with stage 4 pancreatic cancer in 2024. Her experience in the clinical trial that extended her life inspired her to pay it forward to future patients.
“My journey was made easier by researchers who worked really hard 20 years ago,” Leung said. “I hope this will lead to less pain and suffering for those who come later.”
She also feels a connection to Kugel, whose scientific work is informed by her own experience with loss.
“Knowing that Professor Kugel lost her dear husband [Fred Hutch researcher Supriya “Shoop” Saha, MD, PhD,] is heartbreaking. She really gets it,” said Leung.
Both women understand how profoundly cancer can change a family’s life.
“I cannot imagine a more special family to be connected with through this extraordinary honor,” Kugel said. “I am deeply grateful for this vote of confidence, and I will work every day to ensure that this investment makes a meaningful difference for patients and their families.”
For Leung, that is exactly the goal: helping to create a future where a pancreatic cancer diagnosis comes with more effective treatments and more hope.
Jamie Wecker is a writer on the Philanthropy team at Fred Hutch Cancer Center. She has a background in physics and studied science writing at Johns Hopkins University. Before starting her writing career at Swedish Foundation, she also worked in early childhood education and electrical sign fabrication. Reach her at jwecker@fredhutch.org.
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