Lisa M. Coussens, Ph.D., associate director of basic research for the Knight Cancer Institute at Oregon Health & Science University, was selected to serve as a principal investigator on an international pancreatic cancer Dream Team recently announced by Stand Up To Cancer (SU2C) and The Lustgarten Foundation at the annual meeting of the American Association for Cancer Research (AACR), SU2C’s Scientific Partner.
The team will receive $8 million in funding over three years to develop treatments that exploit a patient’s own immune cells to eradicate their cancers.
As part of the project, Coussens, who is also chair of the Department of Cell & Developmental Biology in the OHSU School of Medicine, will oversee a group of Knight Cancer Institute contributors. These researchers, among other things, will use bioinformatics to analyze tumor tissue from all of the patients participating in the projects’ clinical trials. This analysis will provide a detailed profile of how each patient’s tumor responds to one of five experimental treatments included in the study. In addition, the team will explore how the immune cells implicated in pancreatic cancer also might play a role in pancreatitis.
“Being part of this international Dream Team will build significant momentum for our exploration of the role of immune cells in enabling tumors to survive and grow,” Coussens said. “The consortium expands what we can do logarithmically.”
The research conducted as part of the Stand Up To Cancer grant could also ultimately prove relevant for head and neck squamous cell cancers, Coussens said.
The Stand Up To Cancer Dream Team grant will build upon work under way by top OHSU pancreatic surgeons and Knight Cancer Institute scientists who are collaborating through OHSU’s Brenden-Colson Center for Pancreatic Care to develop treatment methods for pancreatic cancer while also exploring the source of pancreatic diseases at the molecular level. The center was formed in 2013 with a $25 million gift from a philanthropic partnership between Norman and Linda Brenden and the Colson Family Foundation. Coussens’ ongoing immune cell research is also bolstered by philanthropy. Among her many roles at OHSU, Coussens holds the Hildegard Lamfrom Chair in Basic Science, a position created as a result of a generous contribution from Columbia Sportswear Chairman Gert Boyle, along with Tim and Mary Boyle, to honor Gert Boyle’s sister, a renowned cancer researcher.
These areas of study are part of the Knight Cancer Institute’s overarching strategy to better understand the molecular underpinnings of cancer to improve early detection and treatment of the disease in its many forms.
“It is gratifying to see Dr. Coussens’ breakthrough work on the immune system’s role in cancer get recognized with the awarding of this Stand Up to Cancer Dream Team grant,” said Brian Druker, M.D., director of the Knight Cancer Institute. “Pancreatic cancer has been a particularly intractable form of the disease and we are optimistic that this concerted research effort will make a meaningful difference for patients.”
Pancreatic cancer is currently the fourth leading cause of death from cancer and is predicted to climb to the second leading cause of death by 2020. Eighty percent of cases aren’t diagnosed until the disease has progressed to late stages when it is difficult to treat.
SU2C has awarded grants to 12 Dream Teams and two Translational Cancer Research Grants. Including Coussens, the Knight Cancer Institute has three top scientists involved in these world- class, multi-institutional projects. Joe W. Gray, Ph.D., associate director for translational research at the Knight Cancer Institute, co-leads a breast cancer Dream Team focused on research for less toxic treatments for breast cancer. Tomasz Beer, M.D., deputy director of the Knight Cancer Institute, is one of six top scientists involved in a research Dream Team to study treatments for advanced prostate cancer.
The SU2C pancreatic cancer Dream Team will be co-led by Elizabeth M. Jaffee, M.D., professor of oncology at the Johns Hopkins University School of Medicine and co-director of the Gastrointestinal Cancers Program at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, Md., and Robert H. Vonderheide, M.D., D.Phil., associate director for translational research at the Abramson Cancer Center of the University of Pennsylvania and the Hanna Wise Professor in Cancer Research at Penn’s Perelman School of Medicine in Philadelphia, Pa. The project will be titled, “Transforming Pancreatic Cancer to a Treatable Disease.”
Pancreatic ductal adenocarcinoma (PDA) is resistant to most forms of therapy and is one of the most deadly types of cancer. The environment that surrounds cancer cells is referred to as the tumor microenvironment, and studies in mice and humans have shown that the PDA tumor microenvironment has unique characteristics that are thought to limit the efficacy of treatment. By understanding the obstacles that prevent the tumor from responding to treatments, it should be possible to develop therapeutic agents to eliminate these barriers, resulting in the effective treatment of PDA.
T cell-based cancer immunotherapy has shown promise for the treatment of a variety of cancer types and was hailed by the journal Science as “Breakthrough of the Year” in 2013. Despite its emerging promise, clinical efforts for immune therapy in PDA have lagged behind. Recent advances in PDA mouse models and in technologies to study cancer-associated immune processes at tumor sites have revealed that major anti-PDA immune responses can occur if antitumor T cell-generating approaches are combined with drugs that block immune suppression in the tumor. Based on promising initial clinical trials, this Dream Team’s goal is to “reprogram” the tumor microenvironment to fuel clinically meaningful anticancer immune responses in patients with PDA.
The Dream Team will use a “convergence” approach by bringing together leading individuals in the fields of immunotherapy, genetics, informatics, biostatistics, regulatory/clinical trials, cancer biology and pathology. This group of experts will apply their efforts toward understanding and treating PDA.
The team will conduct combination clinical trials and establish biomarkers of tumor microenvironment reprogramming. Trials will focus on novel immune-suppressive pathways within the tumor, either in combination with a T cell-activating vaccine or chemotherapy. These trials will also establish a national PDA biobank for identification of immune biomarkers. Preclinical studies in PDA mouse models will be conducted to establish novel multiagent approaches and develop biomarkers that will drive the next generation of clinical trials.
Along with Coussens, Knight Cancer Institute researchers contributing to the Dream Team project will include Adam Margolin, Ph.D.; Andrew Gunderson, Ph.D.; and Christopher Chan, Ph.D.; as well as graduate student Shannon Liudahl.
Researchers on the Dream Team represent patient advocates as well as nine institutions, including the OHSU Knight Cancer Institute. The other participating institutes are: Johns Hopkins University; Abramson Cancer Center of the University of Pennsylvania; Washington University in St. Louis; University of California, San Francisco; NYU Langone Medical Center; Stanford University; University of Cambridge, United Kingdom and Memorial Sloan Kettering Cancer Center.