A Wilmot Cancer Institute researcher has launched an innovative new study, combining radiotherapy and immune therapy as a way to attack pancreatic cancer, a disease known for its dismally low survival rate.
Scott Gerber, Ph.D., received a National Cancer Institute $2 million grant to investigate this new strategy for locally advanced disease. The project is relevant for most patients, who are typically diagnosed after their pancreatic cancer has already begun to spread, making it harder to treat. One of the main problems lies in the microenvironment immediately surrounding the tumor; it consists of toxic proteins that protect cancer cells from being destroyed by the body's own immune system.
The goal is to convert an immune-suppressive tumor microenvironment into one that can fight cancer.
Researchers suspect that stereotactic body radiotherapy (SBRT), which delivers high doses of radiation over a short period of time to control tumors, may prime the immune system to kill cancer cells. SBRT is used to control many types of cancer, and is emerging as a useful pancreatic cancer treatment. To sustain and augment SBRT's anti-tumor activity, Gerber's team is investigating the addition of an immune-activating drug, Interleukin 12 (IL-12). They plan to administer IL-12 with a cutting-edge technology called microspheres, tiny particles that encapsulate the IL-12 and allow scientists to control the release of the drug in slow, continuous manner for 10 to 14 days.
Researchers are studying this combination therapy in a specially designed mouse model for pancreatic cancer.
"Currently we have limited treatment options for individuals diagnosed with pancreatic cancer, even when it is detected early," said Gerber, an assistant professor in the University of Rochester Medical Center Department of Surgery and Microbiology/Immunology. He is also co-director of Wilmot's Center for Tumor Immunology Research. "There's a vital need to develop new strategies and improve existing treatments to increase survival of this disease."
The NCI grant is based on earlier pre-clinical studies conducted by the Gerber Lab, which showed that IL-12 combined with SBRT can reduce tumors or even cure the cancer in mice. The current research builds on those results, focusing on how best to galvanize the immune system and also destroy tumors that have metastasized to the liver, a common occurrence in pancreatic cancer.
Gerber and his team collaborate closely with David Linehan, M.D., the Seymour I. Schwartz Professor and Chair of Surgery at URMC, director of clinical operations at Wilmot, and an international pancreatic cancer expert. Also working on the NCI project is Marvin Doyley, Ph.D., professor of Electrical and Computer Engineering, Biomedical Engineering, and Imaging Sciences at UR. Doyley is an expert in how imaging technology can be used to predict whether drugs can penetrate the complex tissue in the microenvironment and get to the tumor. Another key member on the project team is Haoming (Carl) Qiu, M.D., a Wilmot radiation oncologist who routinely treats pancreatic cancer patients with SBRT. His expertise is pivotal for making sure that the bench science advances to patient care.
"We are very excited about this project and believe that it will eventually have clinical significance for patients," Gerber said. If the current study is successful, the next step is to design a clinical trial for the SBRT/IL-12 combination therapy.
Pancreatic cancer can be difficult to detect because the symptoms are not always obvious and tend to develop and worsen over time. The five-year survival rate for all stages of pancreatic cancer combined is about 9 percent, according to the American Cancer Society.