Luisa Escobar-Hoyos envisions a world where a pancreatic cancer diagnosis is no longer a death sentence.
"Every time I tell people I work on pancreatic cancer, people are like, 'That's a really bad one, right?,'" said Escobar-Hoyos, associate professor of therapeutic radiology at Yale School of Medicine.
Pancreatic cancer is among the deadliest cancers, with a five-year survival rate of just 13%. It's often called "the silent disease" because it can be difficult to detect it in its earliest stages. For Escobar-Hoyos, the disease isn't just a professional interest. It's also become deeply personal. Her mother was diagnosed with Stage 4 pancreatic cancer in December 2023.
"She knew that death was coming, and that it was more a matter of time," said Escobar-Hoyos, who has secondary appointments in Medical Oncology and Hematology and in the Department of Molecular Biophysics and Biochemistry in Yale's Faculty of Arts and Sciences. "I hated that feeling of knowing a clock was ticking."
After 14 months of treatment, her mother died. Escobar-Hoyos learned many lessons through the experience, but above all, she learned the importance of hope. "One thing you can never take away from a patient is their hope," she said. "Latching onto hope was very important for all of us as a family."
Today, Escobar-Hoyos is channeling that hope into her work. In her lab, she and her team are developing biomarker-guided therapies designed to outsmart the most aggressive tumors. "Even if these new treatments can't save my mom, I'm hopeful because they show that this disease might not be a death sentence for others in the future," she said.
In an interview, Escobar-Hoyos discusses her lab's work, the challenges within pancreatic cancer treatment, how patient outcomes can be improved, new drugs offering hope for patients, and more.
The interview has been edited for length and clarity.
Why is pancreatic cancer diagnosis so deadly?
Luisa Escobar-Hoyos: It's multiple things. Unfortunately, it's a very silent malignancy. My mom had zero symptoms. She didn't lose weight. She just felt a little bit of pain after she ate, and it turns out she had a monster inside of her. It's not like we have a routine screening test, like a mammogram for breast cancer. We can't just take a quick image or a small piece of the pancreas to check on it regularly. This often leads to late diagnosis.
We've also known for many years that these tumors have a low "mutational burden," meaning they have very few genetic mutations. That's bad for two reasons. First, in order for immune cells to see cancer cells as "bad," they need to recognize them as faulty or mutated. With pancreatic cancer, because people don't have that many mutations, the immune system doesn't see them as being faulty or bad. The other problem with having low mutational count is that it's hard to make targeted therapies because there aren't that many mutated proteins.
What are some of the challenges inherent in pancreatic cancer treatment?
Escobar-Hoyos: For at least 85% of patients diagnosed with disease, it's not operable. That's the first challenge. We only have chemotherapy for them, and we need to match them with the right chemotherapy. But sometimes these patients are frail. They've lost weight. They're in their 60s or 70s. Also, while the disease starts very silent, it rapidly progresses. You're dealing with a monster that's kind of sleeping but then wakes up very soon.
Your lab, the Escobar-Hoyos Lab, operates at the intersection of pathology, RNA biology, and immuno-oncology. Tell us about the work you're doing to develop novel therapies for pancreatic cancer.
Escobar-Hoyos: We have different strategies to develop novel therapies. One of them likely won't make a difference; we need combinations of them. So, we're betting on these multiple strategies.
First, we're studying how cancer cells "edit" their RNA messages before they're turned into proteins. Normally, one gene can be used to make several different proteins, depending on how its RNA is cut and stitched together - a step called RNA splicing. Pancreatic cancer often takes advantage of this process to make protein versions that help the tumor grow and that can help it evade newer targeted drugs, including some KRAS inhibitors. For a long time, researchers didn't focus much on splicing as a major way cancer resists treatment because we hadn't looked closely enough at the cell's RNA layer. Now that we are, we're finding new, cancer-specific protein targets. Our goal is to develop therapies that go after these harmful proteins produced by abnormal splicing.
We're also studying why some cancers are hard for the immune system to "see." Many successful cancer immunotherapies work best when tumors have lots of DNA mutations, because mutations can create new protein fragments, called antigens, that immune cells recognize as foreign. But some tumors, including many pancreatic cancers, have few mutations, so they don't show many obvious targets. What we found is that these tumors often switch on a protein that's normally used only during early embryonic development and is usually turned off in healthy adult tissue. We're trying to use pieces of that protein as targets for a vaccine, so the immune system can learn to recognize and attack tumor cells, even without relying on mutations.
What's making you hopeful about the future of pancreatic cancer treatment?
Escobar-Hoyos: First, awareness. More and more people now know about pancreatic cancer. We haven't changed the survival rates in over 50 years. Awareness from communities, from hospitals, from the government, and from foundations is what's going to allow us to funnel resources to study and understand more of this disease.
Second, breakthroughs with targeted therapies like KRAS inhibitors. The RAS family of genes plays a critical role in regulating cell growth and division. KRAS is the most common subtype and when mutated it promotes the development of many cancers, including pancreatic cancer. For decades, we thought of KRAS as undruggable. But there are new drugs coming out like KRAS inhibitors making a big splash in the news. We have phase 3 clinical trials for pancreatic cancer with this KRAS inhibitor showing that the patients respond, and that the tumor shrinks. This is giving me hope.
The other thing that gives me a lot of hope is the research going on in my lab. We're coming up with targeted therapies and immunotherapies that, while they're still at the experimental level, our preclinical data from mice and patients' tumors grown in the lab are showing that they're working. The memory and the loss of my mom have ignited in me more hope and more energy to push this forward.
