Pancreatic cancer is a rare tumor, accounting for only about 3% of cancer cases, but it is one of the most deadly. Over 67,000 Americans will be diagnosed with pancreatic cancer in 2025, and about 50,000 will pass away this year because of the disease. Up to 80% of pancreatic cancers aren’t diagnosed until they are at highly advanced stages, because the disease is typically asymptomatic early on.
Researchers at Hopkins have made strides in pancreatic cancer research, both in understanding age-related differences in prognosis and working on the development of a vaccine for patients at high risk of developing the disease. Fueled by personal commitment to the work and vital support from federal funding, scientists like Dr. Daniel Zabransky and Dr. Elizabeth Jaffee are working to unravel the biology of pancreatic cancer and reshape its future.
Zabransky, an assistant professor of oncology at the School of Medicine, has been involved in research since his undergraduate years. Now a medical oncologist specializing in gastrointestinal cancers such as pancreatic tumors, Zabransky leads a research group that aims to elucidate why pancreatic cancer is more common in older patients.
The median age at diagnosis for pancreatic cancer is 71 years. Most patients are diagnosed at age 55 or older. Zabransky’s previous work demonstrated that age-related changes in non-malignant cells could drive growth and progression of other cancers. In particular, his team is now investigating how pancreatic fibroblasts, cells that contribute to connective tissue formation, drive many of these age-related changes.
“We showed that pancreatic fibroblasts, as they age, get new properties, and they change what they're sending out into their environment in terms of the signals. And we identified a molecule, GDF 15 — Growth Differentiation Factor 15 — which goes up with aging in pancreatic fibroblasts and in the pancreas. That ended up being a molecule that drove pancreas cancer growth and invasiveness,” Zabransky explained in an interview with The News-Letter.
Jaffee, a professor of oncology and deputy director of the Sidney Kimmel Comprehensive Cancer Center at Hopkins, highlighted some of her work — funded by the U.S. Department of Defense — which focuses on the development of a pancreatic cancer vaccine to address the limitations of current pancreatic cancer treatments.
Pancreatic cancer progression is dependent on Kirsten rat sarcoma virus (KRAS) mutations, which code for the K-Ras protein, a key protein in the signaling pathways of the cell cycle. Specifically, KRAS mutations impact the Ras/MAPK pathway, which can cause abnormal or uncontrolled cell division in the human body. KRAS mutations account for about 85% of pancreatic cancer cases, which has motivated the use of KRAS inhibitors for pancreatic cancer treatment.
“The problem with targeting [pancreatic cancer] with a drug is that the drug only works for a short period of time, six to 12 months, and then resistance occurs,” Jaffee elaborated in an interview with The News-Letter.
To combat this, Jaffee and her team are working on a vaccine for pancreatic cancer. The vaccine adds additional agents that can modify T-cells to make them respond to tumor cells more efficiently. These agents are inspired by immune checkpoint modulators, which have shown great promise in many cancer immunotherapies, but do not function in pancreatic cancer on their own because immune cells cannot recognize mutated KRAS.
“We’re alerting the immune system to recognize mutated KRAS,“ Jaffee explained. “[The immune system] makes these T-cells that now we can give with immune agents to make T-cells function even better. The other [part] is to try to bring in the immune system in collaboration with these KRAS inhibitors so that the KRAS inhibitors can have more longevity.”
Jaffee then described how her work connected with Zabransky’s, highlighting new research efforts to understand more subtle differences in pancreatic cancer development with age.
“We're very concerned about younger people getting pancreatic cancer. We've even started to see people in their early 20s, and that's really alarming, because we don't screen to identify people with cancer early, until they are between 40 and 50, so we're going to miss these people,” she emphasized.
Both Zabransky and Jaffee emphasized that none of this work, or any continued innovation in the field, would be possible without federal funding.
“The funding that we get allows us to ask big questions, to take risks and to really learn about the disease without having to think about how we are going to make more money off what we are doing immediately,” Zabransky explained. “The ability to have that longer-term mindset and really understanding the disease has been transformational in our ability to think about, ‘how will we one day help a patient?’”
Jaffee elaborated further on this subject, highlighting the momentum of current cancer research and the role federal funding has played in maintaining it.
“The technologies are advancing so quickly that we are able to begin to understand a cancer in its basically natural environment, so this is going to allow us to develop new therapies and to make them personal to patients, even more so than we already can today [...] However, we have one major problem right now, and we can't forget about that, and that is that this current environment, politically, is squashing what we can do in science,” Jaffee said.
Both Zabransky and Jaffee echoed the importance of long-term investment in scientific research and the flexibility it provides. In particular, Jaffee discussed how it took decades of NIH investment to make progress in immunotherapies for cancer, and that NIH funding has sped up technological innovation to push forward further progress in the field.
Funding cuts and tariffs from the Trump administration have already directly impacted Jaffee’s work. These impacts ripple outwards, having downstream effects on graduate students, postdoctoral positions and undergraduate research opportunities. At Hopkins alone, the most recent round of grant cuts totals about $6.5 million.
“We developed our vaccine ourselves, but there's only one company that really will make the vaccine for us that we can give to patients right now, and that's in Germany. And yesterday, another lot of this vaccine came to the U.S. border, and we were told that we had to pay an extra $13,000 because of the tariffs now. I don't know where to get that extra $13,000,” Jaffee explained.
The cuts in federal funding for research have had devastating impacts on clinical research. For clinical trials that are currently underway, recent federal policy changes have impacted their continued access to funding. At least 47 grants awarded by the National Cancer Institute were canceled in the first month of federal policy changes. Clinical trials abroad on a larger scale, originally funded by the U.S. Agency for International Development, have been stopped almost entirely, including trials for a screening and treatment method for cervical cancer in Malawi. Jaffee highlighted that her clinical trials and patients were also impacted.
“If the NIH tells us today that they're going to stop our funding, like they've done with Harvard and with Columbia and with other universities, I will have to say to patients, ‘I'm sorry; this study is funded by my grant. They just stopped it.’ They give you a day. That's what's happening right now,” Jaffee emphasized.
