Read time 2 minutes | Wednesday, 2 April 2025
The Takeaway
CSHL Professor David Tuveson and Research Investigator Claudia Tonelli have found a way to “intercept” pancreatic cancer. By inhibiting the cancer gene FGFR2, they were able to slow tumor formation. By targeting the FGFR2 and EGFR proteins, they were able to prevent pancreatic cancer from forming in the first place.
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Pancreatic cancer is projected to become the second-deadliest cancer by 2030. By the time it’s diagnosed, it’s often difficult to treat. So, for both individual patients and the general population, fighting pancreatic cancer can feel like a race against time. Cold Spring Harbor Laboratory (CSHL) Professor and Cancer Center Director David Tuveson offers a telling analogy:
“We all have moles on our skin. Most of your moles are fine. But some of your moles you have a dermatologist looking at to make sure it’s always fine. They may take it out and send it to the pathologist to ask, ‘Is this an early melanoma, a melanoma in situ?’ Now, that’s just what you can see. Imagine that in your pancreas—because that’s the reality. We all have early versions of cancer in many tissues at all times.”
Now imagine treating those “early versions” in the pancreas—before they become cancerous. A new discovery at the CSHL Cancer Center could help make this possible. Tuveson and Research Investigator Claudia Tonelli have found a way to effectively “intercept” pancreatic cancer. To understand how it works, we need to first understand a little bit about pancreatic cancer genetics.
“Over 95% of pancreatic cancer patients have mutations in KRAS,” Tonelli explains. “It’s the driving oncogene in this disease. We discovered that another gene, FGFR2, plays a role in enhancing mutant KRAS signaling in pancreatic cancer. When that happens, those ‘early versions’ of pancreatic cancer become much more aggressive.”
photo of Claudia Tonelli in a laboratory
The study’s lead author, Claudia Tonelli, is a research investigator in the Tuveson lab. Tonelli has a Ph.D. in molecular medicine from the European Institute of Oncology in Milan, Italy.
Tonelli and Tuveson observed this outcome in mice and organoids—lab-grown versions of human pancreatic tissue. Of course, the researchers weren’t just having a look. Their goal was to stop the pancreatic tissue from becoming cancerous. Because FGFR2 is a known oncogene in other cancers, several inhibitors are already used in the clinic today.
When Tonelli and her colleagues inhibited FGFR2 at precisely the right moment, they got the results they wanted. Tumor formation slowed significantly. When they targeted FGFR2 along with EGFR—a protein known to be overactive in pancreatic cancer—they saw even better results. Fewer “early versions of cancer” formed in the first place.
“With an increasing number of FGFR2 inhibitors entering the clinic, our study lays the foundation to explore their use in combination with EGFR inhibitors for pancreatic cancer interception,” Tonelli says. Patients with a family history of pancreatic cancer would likely be among the first candidates to receive such treatments.
For now, fighting pancreatic cancer remains a race against time. But with this discovery, the day may soon come when time is on our side.
Written by: Samuel Diamond, Editorial Content Manager | diamond@cshl.edu | 516-367-5055
Funding
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National Institutes of Health, The Lustgarten Foundation, Thompson Family Foundation, Pershing Square Foundation, CSHL-Northwell Health Affiliation, Northwell Health, Cold Spring Harbor Laboratory Association, Simons Foundation, American-Italian Cancer Foundation, National Cancer Institute
Citation
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Tonelli, C., et al., “FGFR2 Abrogation Intercepts Pancreatic Ductal Adenocarcinoma Development”, Cancer Research, April 2, 2025. DOI: 10.1158/0008-5472.CAN-24-4576
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The Takeaway
CSHL Professor David Tuveson and Research Investigator Claudia Tonelli have found a way to “intercept” pancreatic cancer. By inhibiting the cancer gene FGFR2, they were able to slow tumor formation. By targeting the FGFR2 and EGFR proteins, they were able to prevent pancreatic cancer from forming in the first place.
Principal Investigator
David Tuveson#### David Tuveson
Professor
Roy J. Zuckerberg Professor of Cancer Research
Cancer Center Director
M.D., Ph.D., Johns Hopkins University, 1994
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