Kenneth Shroyer, MD, PhD
Stony Brook University
Research Project: Keratin 17 Is a Novel Actionable Target in Pancreatic Ductal Adenocarcinoma
Award: 2018 Pancreatic Cancer Action Network Translational Research Grant
Award Period: July 1, 2018 – June 30, 2021
Dr. Shroyer is a surgical pathologist, cytopathologist and chair of the department of pathology at Stony Brook Medicine. Dr. Shroyer earned his PhD and MD at the University of Colorado Graduate School and School of Medicine, respectively. Over the past two decades, he has engaged in transformative research to address concepts on the origin of cervical cancer and other solid tumors. More recently, he shifted his focus to the discovery of molecular factors that drive tumor aggression and prognostic biomarkers (biological clues to predict patient outcomes) of pancreatic cancer.
Members of his team, including his co-investigator and former graduate student, Dr. Luisa Escobar-Hoyos (recipient of a 2017 Pathway to Leadership Grant from PanCAN), found that the detection of a protein called keratin 17 (K17) is more accurate than a clinical or pathological assessment to predict pancreatic cancer patient survival. Furthermore, his team found that K17 causes resistance to chemotherapeutic agents, drives tumor aggression and leads to biological changes that could be targeted with drugs. Dr. Shroyer’s team is dedicated to the development of new biomarker-based treatment strategies that will ultimately provide more effective treatments for pancreatic cancer patients.
Following years of limited progress in the development of effective methods to treat pancreatic cancer, it was recently discovered that there are genetic subtypes of the disease that correspond with patient survival. Most aggressive is the basal subtype, which shows increased resistance to currently available chemotherapeutic agents. Dr. Shroyer and his team found the basal subtype, representing 50 percent of cases, is characterized, in part, by the expression of keratin 17 (K17). K17 is a protein that is expressed during the development of the embryo, is turned off in most normal adult tissues but is turned back on in many cancers, including the basal subtype of pancreatic cancer.
Members of the Shroyer lab recently found that this protein has surprising properties, including the ability to move into the nucleus of cancer cells, where it targets proteins, including p27, that normally control cell division. As a result, the movement of K17 into the nucleus triggers processes that cause tumor cells to divide and cancer to grow. This project is designed to test the idea that the investigators may be able to develop new and more effective ways to treat pancreatic cancer by blocking K17 to control its movements and functions.
In addition, they intend to determine whether targeting K17 with drugs would work as an effective new treatment with fewer toxic side effects. Furthermore, they will find out if this approach could enhance the effectiveness of current chemotherapeutic drugs that are already widely used to treat this disease. If they are successful, Dr. Shroyer believes they will have uncovered an “Achilles heel” for the most aggressive form of pancreatic cancer and identified new ways to tackle this disease and improve patient survival.