2017 GRANTEE: Timothy C. Wang, MD
Co-principal Investigator: Paul Oberstein, MD
Research Project: Targeting Cholinergic Receptors to Suppress Pancreatic Cancer
Award: 2017 Tap Cancer Out – Pancreatic Cancer Action Network Translational Research Grant
Award Period: July 1, 2017 – June 30, 2019
Dr. Wang is the Silberberg Professor of Medicine, chief of the digestive & liver diseases and director of the gastrointestinal cancer program at Columbia University Medical Center. He is the immediate-past president of the American Gastroenterological Association. He received his BA from Williams College and his MD from the Columbia College of Physicians & Surgeons. Dr. Wang has led an independent research lab for over 25 years that focuses on the relationship between inflammation, stem cells and cancer, and on the molecular mechanisms of gastrointestinal carcinogenesis. Dr. Wang received a Merit Award from the National Institute of Diabetes and Digestive and Kidney Diseases, the Outstanding Investigator Award from the National Cancer Institute and an Innovative Grant from the Pancreatic Cancer Action Network.
Dr. Oberstein is an assistant professor of medicine in the division of hematology/oncology at Columbia University Medical Center. He received his BS from University of Maryland and then earned his MD from Ohio State University College of Medicine. He underwent his internal medicine and hematology/oncology training at Temple University and Columbia University, respectively. In 2015, he earned a master’s degree in biostatistics from Columbia. Dr. Oberstein’s primary research training has taken place in the laboratory of Kenneth Olive, PhD, also a former Pancreatic Cancer Action Network research grant recipient.
Pancreatic tumors are known to be surrounded and supported by a dense stroma, which is a complex network of a variety of cell types. Nerves are a component of the stroma, and signaling coming from nerves has been shown to promote the growth of other kinds of cancer.
Drs. Wang and Oberstein and their colleagues were surprised to discover that cellular signaling coming from a particular type of nerves, called cholinergic nerves, suppresses pancreatic cancer growth, rather than supporting it. Specifically, pancreatic cancer growth and metastatic spread are impeded by a protein called the muscarinic receptor that is present on nervous system cells.
To better understand the suppression of pancreatic cancer growth by muscarinic receptors, Drs. Wang and Oberstein and their research teams will utilize a drug that is a muscarinic agonist – meaning that it enhances the activity of the muscarinic receptor. They will determine whether the drug blocks pancreatic cancer growth and metastatic spread in mouse models of the disease and will also determine its function in combination with chemotherapy. In addition, the researchers aim to scrutinize the exact mechanisms of how the muscarinic agonist works.
Finally, Drs. Wang and Oberstein will conduct a pilot clinical trial of 15 patients who will receive the muscarinic agonist as an oral drug for at least two weeks prior to undergoing surgery to remove their pancreatic tumor. This trial will confirm the safety of the drug and determine its effect on biomarkers that indicate the rate of tumor growth, as well as provide a foundation for future clinical trials.