2017 GRANTEE: Sunil R. Hingorani, MD, PhD
Fred Hutchinson Cancer Research Center
Research Project: Combining Stromal Disruption and Relief of Immune Suppression to Treat PDA
Award: 2017 Pancreatic Cancer Action Network Precision Medicine Targeted Grant
Award Period: July 1, 2017 – June 30, 2019
Dr. Hingorani is a medical oncologist and cancer biologist specializing in pancreas cancer. He is a member with joint appointments in the clinical research and public health sciences divisions at Fred Hutchinson Cancer Research Center and professor in the department of medicine, division of medical oncology at University of Washington School of Medicine. He received a BS in molecular biophysics and biochemistry from Yale College and a PhD in cellular and molecular physiology and an MD from Yale University. He completed a fellowship in hematology and oncology at Dana-Farber Cancer Institute in Boston and performed postdoctoral research at MIT.
Dr. Hingorani is the founding director of the Pancreas Cancer Specialty Clinic at the Seattle Cancer Care Alliance, a real-time multidisciplinary clinic that serves as the focal point for a comprehensive translational research program in pancreas cancer, the Center for Accelerated Translation in Pancreas Cancer (CATPAC), which he also directs. Dr. Hingorani has previously been awarded two research grants from the Pancreatic Cancer Action Network and is a member of our Scientific & Medical Advisory Board.
In addition to being hard to detect, pancreatic cancers are also unusually resistant to all current forms of chemotherapy and radiotherapy. Recently, Dr. Hingorani and others have begun to identify previously unrecognized processes in the tumor that help to explain their unique behaviors. What the researchers have come to appreciate is that a pancreatic tumor represents a coordinated evolution of a cancer cell together with a number of other cell types and processes that are complicit in its survival. Thus, attacking these supporting processes offers new opportunities for therapies.
For example, Dr. Hingorani and his colleagues have identified extremely high pressures inside these cancers that cause the majority of blood vessels inside them to collapse; this makes it difficult to get chemotherapies into the tumor, because they are delivered via the bloodstream. The major component of the supporting matrix inside the tumors that causes these elevated pressures is hyaluronic acid (HA). A strategy to degrade HA inside pancreatic cancers has led to blood vessels opening more widely and chemotherapy entering at higher and more effective concentrations.
The research team has also identified several classes of immune cells that are present from the earliest stages of pancreatic cancer development and that actually help support its growth, rather than inhibit it (by turning off the positive [effector] arm of the immune system). By attacking these cells, Dr. Hingorani and others have found that effector immunity can be awakened and actively engage in the fight against this cancer.
In this proposal, Dr. Hingorani will investigate different combination strategies of matrix-targeting and immune suppressor cell-targeting agents and rigorously measure their effects. The top regimen(s) will then also be tested with and without conventional chemotherapy. In the end, the best regimen to emerge from these studies will be ready for large trials in patients and will hopefully establish a new standard of care that is more effective than the current paradigm.