GRANTEE: David Linehan, MD
University of Rochester
Co-Principal Investigator: Brian Wolpin, MD, MPH, Dana-Farber Cancer Institute
Research Project: Targeting Macrophages to Improve Chemotherapy in Metastatic Pancreas Cancer
Award: 2016 The Shirley Sadoff – Pancreatic Cancer Action Network Research Acceleration Network-2 Grant
Award Period: July 1, 2016 – June 30, 2019
Dr. Linehan graduated from the University of Massachusetts Medical School before fulfilling his internship and residency at Deaconess-Harvard Surgical Service. He completed a research fellowship at Brigham and Women’s Hospital before he became chief resident in surgery at Beth Israel Deaconess Medical Center. Dr. Linehan finished his medical training as the Kristin Ann Carr Fellow in Surgical Oncology at New York’s Memorial Sloan-Kettering Cancer Center. He currently serves as chair of the department of surgery at the University of Rochester, where he holds the Seymour I. Schwartz Professorship in Surgery. Dr. Linehan received a Translational Research Grant from the Pancreatic Cancer Action Network in 2015.
Dr. Wolpin is an associate professor of medicine at Harvard Medical School and the co-director of the pancreas and biliary tumor center at the Dana-Farber Cancer Institute. He attended Harvard Medical School and then conducted his residency in internal medicine and fellowship in medical oncology at Brigham and Women’s Hospital and Dana-Farber Cancer Institute, respectively. He then completed a master’s degree in public health at the Harvard School of Public Health, with an emphasis on epidemiology, biostatistics and study design.
A prominent characteristic of pancreatic tumors is a dense and complex stroma, which is made up of various types of cells that surround and infiltrate the tumor. Immune and inflammatory cells are prevalent within the stroma, and these cells help “hide” the tumor from the immune system, blocking its ability to recognize and attack the cancer cells.
Dr. Linehan’s 2015 Translational Research Grant focused on blocking the activity of a protein called CCR2 that is involved in the stromal cells’ ability to be recruited to the tumor and to block the immune system. In May 2016, Dr. Linehan published a study in the prestigious journal Lancet Oncology that describes encouraging results from a phase 1b clinical trial of the CCR2 inhibitor (PF-04136309, from Pzifer) in pancreatic cancer patients with locally advanced disease (their tumor has begun to spread within the pancreas and surrounding blood vessels, but hasn’t metastasized to other organs yet).
Based on promising results from this early-phase trial, Drs. Linehan and Wolpin will conduct a large, multi-center phase 2 clinical trial testing the CCR2 inhibitor in combination with a chemotherapy regimen (gemcitabine and nab-paclitaxel) in patients with metastatic pancreatic cancer. In conjunction with the clinical trial, they will collect blood, bone marrow and tumor biopsies from the patients. These specimens will be scrutinized in order to identify which biomarkers, or biological clues, are present that may predict which patients will respond best to this treatment, allowing a personalized medicine approach. They will also analyze biomarkers that may predict or help explain the mechanism of tumor resistance to the treatment. Drs. Linehan and Wolpin have assembled a team of expert physician-scientists at several high-volume pancreatic cancer centers that will share biopsies to measure immune responses and see how genetic changes in both tumors and immune cells can be used to perfect this new approach to treat pancreatic cancer.