Each year at our Hirshberg Symposium on Pancreatic Cancer, we share the latest progress in pancreatic cancer research and treatment. At our 2025 Symposium, Dr. Timothy Donahue, Chief of Surgical Oncology at UCLA and Director of the Hirshberg Center for Pancreatic Diseases, offered a hopeful and inspiring look at how far we’ve come and where science is taking us next.
For the first time in over a decade, the FDA approved a new first-line treatment for pancreatic cancer: Nalirifox, a combination of four chemotherapy agents. This approval is especially meaningful for UCLA, where faculty member Dr. Zev Wainberg led the pivotal clinical trial. Nalirifox gives oncologists another tool for patients with metastatic disease and underscores the importance of participating in clinical trials, where tomorrow’s treatments are tested today.
As of the 2023 NCCN Guidelines for Patients, it is recommended that every pancreatic cancer patient have genetic and, more encompassing, genomic testing to identify treatment opportunities. Testing can identify germline (inherited) and somatic (tumor) genetic mutations. For those with BRCA mutations, for example, a class of drugs called PARP inhibitors may be effective. Patients with microsatellite instability or other specific mutations might benefit from immunotherapy. Knowing your tumor’s biology can lead to more targeted and potentially less toxic treatments.
KRAS mutations are among the most common and challenging drivers of pancreatic cancer. Historically considered “undruggable,” new KRAS inhibitors are finally entering the clinic. UCLA is participating in several early-phase trials using these targeted therapies, sometimes in combination with chemotherapy or immunotherapy. These studies, at UCLA and beyond, offer new hope for a subset of patients whose tumors carry this specific mutation.
One of the most exciting areas of progress involves patients with borderline resectable tumors, those close to critical blood vessels. While chemotherapy has long been used to shrink tumors before surgery (called neoadjuvant therapy), UCLA researchers are taking it a step further. In one trial, Dr. Donahue’s team added an immune checkpoint inhibitor to standard chemo. Initial results showed little added benefit, but tissue analysis revealed that tumors were increasing production of adenosine, a molecule that suppresses immune response. This discovery led to a new approach: adding a CD73 inhibitor to block adenosine and increase the activity of the immune checkpoint inhibitor.
The early results are promising. Among the first 14 patients who completed this new triple-combination therapy and underwent surgery, no patients showed disease progression during treatment, all tumors shrunk on imaging, all lymph nodes were cancer-free, and 42% had a major pathologic response, showing dramatic tumor cell death under the microscope.
“This is one of the most encouraging signals we’ve seen,” said Dr. Donahue. UCLA hopes to expand this into a larger, randomized clinical trial.
The novel mRNA vaccine for pancreatic cancer developed at Memorial Sloan Kettering has expanded its phase II clinical trial to include sites across the US and the globe. After surgery, patients’ tumors are sent to Germany, where scientists develop a personalized vaccine targeting the unique mutations in their tumor’s DNA. The vaccine is then administered along with chemotherapy and immunotherapy in hopes of stimulating a powerful, customized immune response, a new frontier in personalized cancer care.
As 2025 unfolds, one thing is clear: research is transforming the outlook for people facing pancreatic cancer. From newly approved treatments to personalized vaccines, Dr. Donahue’s update offers patients and families much-needed hope.
The Hirshberg Foundation is proud to support this cutting-edge work through funding, collaboration, and patient education. By working together, we can advance towards a future where early detection and proactive prevention truly transform outcomes for those facing pancreatic cancer.
