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by Erin Post  —  Aug 17, 2026

For decades, pancreatic cancer research was defined by what seemed to be impossible. Researchers couldn’t target the mutations in the RAS family of proteins that drive more than 90% of cases. Often described as a “smooth ball,” the RAS protein is frustratingly free of any pockets or divots that would allow a drug to bind to it. Researchers deemed it “undruggable.”
Not anymore. Thanks to the dedication of generations of scientists and researchers, we’ve reached a tipping point where KRAS has been unlocked. For a disease that has for decades seen limited treatment options and a five-year survival rate that is the lowest of all major cancers, the future looks bright.
Today, more than 75 distinct drugs are in clinical trials targeting RAS proteins and we now are closer than ever to the first RAS-targeting therapy for patients with pancreatic cancer.
“This is a defining moment in pancreatic cancer research,” said PanCAN President and CEO Julie Fleshman, JD, MBA. “Today’s advances are the result of years of work by researchers, patients who participated in clinical trials and advocates who raised their voices on behalf of every person diagnosed with this disease, pushing for public and private investment in research. PanCAN is the organization leading the way into this new era of treatment.”
Breakthroughs happen when an entire field moves as one community to share knowledge, bridge gaps and accelerate progress. PanCAN has been and will continue to be the backbone of that effort:
When PanCAN was founded in 1999, the five-year survival rate was a dismal 4%, there was little public awareness and few scientists studying the disease. Recognizing the need to expand the pancreatic cancer field and attract and support early-career investigators, PanCAN launched a competitive, peer-reviewed grants program for basic, translational and clinical research in pancreatic cancer to build the field and accelerate progress and innovation.
KRAS mutations drive pancreatic cancer, but how? What does this look like at a cellular level? What changes are seen at each stage of progression? A mouse model that allows researchers to start answering these questions was described for the first time in a Cancer Cell paper in 2003. This work, led by David Tuveson, MD, PhD and Sunil Hingorani, MD, PhD, was partially funded by PanCAN. The model, which was freely shared with academic groups, has become the benchmark resource for a variety of laboratories around the world.
At a time when KRAS was considered undruggable, and no pharmaceutical company was developing therapies to target it, PanCAN invested anyway, because we believed this work would be critical for treating patients. We began to fund grants exploring RAS inhibition, seeding the field with researchers who go on to mentor future scientists.
One example: Channing Der, PhD, a member of the research team in the 1980s who discovered the RAS gene, received in 2012 his first grant specifically focused on pancreatic cancer. It came from PanCAN. His goal: Figure out how to turn off the signaling fueling cancer growth. At the time, he called it a “new direction in treating cancer known as targeted therapies.” Fast forward to today and we have dozens of those targeted therapies in the pipeline. And Dr. Der is one of the most influential researchers in the space.
After successfully advocating for passage of the Recalcitrant Cancer Research Act which included prioritization of RAS, PanCAN partners with the National Cancer Institute’s new RAS Initiative to grant KRAS Awards to seven early career investigators. These researchers start to dig into all angles of this family of genes — from structural studies of KRAS and exploring specific mutations like KRAS G12D to looking at small molecules that bind to KRAS and KRAS protein production. These studies begin to unlock KRAS — work guided by PanCAN’s Community for Progress and its philosophy of collaboration and mentorship.
Andrew Aguirre, MD, PhD, received his first PanCAN fellowship as a graduate student. When he started his independent lab at Dana-Farber, his hiring committee asked why he wanted to study RAS — there were no drugs, and no one expected there would be. A PanCAN Fellowship Award and later a Catalyst Grant funded in memory of Skip Viragh gave him the financial footing to keep going. Today he co-directs Dana-Farber’s Center for RAS Therapeutics. And this leadership has fostered the next generation of research talent: One of Dr. Aguirre’s PhD students, Julien Dilly, MS, recently received a PanCAN Fellowship Award to study the next frontier for RAS-targeting therapies: Understanding why pancreatic cancer cells develop resistance to treatment over time.
PanCAN’s $3.8 million Therapeutic Accelerator Award was awarded to Verastem Oncology for their early-stage clinical trial testing a treatment combination targeting signaling pathways that get activated by and alongside mutant KRAS. We saw the gap at the time: Pancreatic cancer research was risky and expensive, so the goal was to incentivize pharma and biotech companies to prioritize new pancreatic cancer therapies and conduct early-stage clinical trials.
The next step: Bring top researchers together to learn everything we can from this work. Through our Therapeutic Accelerator Collaborative, PanCAN provided direct support for academic researchers to better understand the investigational treatment combination being evaluated by Verastem — how it works and how to make it work better — with KRAS at the center of all the studies. Experiments with several inhibitors, including daraxonrasib, the RAS-targeting therapy now under review with the FDA, were part of this project.
One of the Collaborative Award recipients was Marina Pasca di Magliano, PhD, who was initially funded by PanCAN via a Career Development Award in 2009. Now a member of our Scientific and Medical Advisory Board, Dr. Pasca di Magliano has pioneered a way to turn mutant KRAS on and off in a mouse model — a critical tool that shows the effects of completely eliminating mutant KRAS signaling.
By bridging gaps and making connections, PanCAN continues to build the research ecosystem. Our Community for Progress creates opportunities for mentorship while our annual Scientific Summit brings leading researchers together with industry partners, patient advocates and donors to collaborate, share knowledge and accelerate progress.
As drugs in the pipeline move forward, we look to the next challenges: How to combat resistance to targeted therapies, how to match patients to the optimal treatment for them, how to make sure patients experience fewer side effects and enjoy the best quality of life possible. The data needed to unlock this next generation of treatments — patient histories, risk factors, tumor profiles, treatment outcomes, side effects — is often housed within individual institutions. No single center sees enough patients to identify all the subtypes of this disease on its own. Until that data is connected at population scale, the field’s most important insight — that pancreatic cancer is many diseases, not one — cannot be fully acted on.
PanCAN’s SPARK Research Data Platform solves for this — linking tumor profiles, clinical outcomes, and patient experiences from PanCAN’s flagship initiatives into a single ecosystem accessible to investigators across academia, biotech and pharma.
It’s one key initiative as PanCAN leads the way into this new era of treatment.
“Our goal is to continue to bring all stakeholders together to accelerate progress — funding early career investigators and innovative research projects, convening the research community, advocating for federal research funding,” said Fleshman. “And always, we put patients at the center of everything — ensuring their voices guide everything we do.”
Read part two of our Unlocking KRAS series, The Power of Advocacy. Learn more about how PanCAN built a grassroots advocacy movement that has helped get us to this tipping point.
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