Pancreatic Cancer Action Network-AACR Research Acceleration Network Grants

The goal of the Pancreatic Cancer Action Network-AACR Research Acceleration Network (RAN) Grants is to provide funding and strategic assistance to research projects with the potential to double survival for pancreatic cancer by the year 2020. Projects must be implemented by multi-institutional teams and include a clinical component with an endpoint relevant to improving the detection or treatment of pancreatic cancer.

2015 Grantees

Developing an algorithm for Molecular Tailored Therapy
Jonathan R. Brody, PhD
Lead Principal Investigator

Jonathan R. Brody, PhD

Associate Professor and Director of Surgical Research
Thomas Jefferson University
Philadelphia, Pennsylvania

Christopher Albanese, PhD
Co-Principal Investigator

Christopher Albanese, PhD

Professor of Oncology and Pathology
Georgetown University Medical Center
Washington, D.C.

Subha Madhavan, PhD
Co-Principal Investigator

Subha Madhavan, PhD

Director, Innovation Center for Biomedical Informatics
Georgetown University Medical Center
Washington, D.C.

Emanuel F. Petricoin III, PhD
Co-Principal Investigator

Emanuel F. Petricoin III, PhD

Professor and Co-director, Center for Applied Proteomics and Molecular Medicine
George Mason University
Fairfax, Virginia

Michael J. Pishvaian, MD, PhD
Co-Principal Investigator

Michael J. Pishvaian, MD, PhD

Assistant Professor in Hematology/Oncology
Lombardi Comprehensive Cancer Center
Washington, D.C.

Research
The team previously conducted a pilot trial that demonstrated the feasibility of delivering Molecularly Tailored Therapy (MTT) for metastatic pancreatic cancer patients. In this project, they are evaluating the benefits of MTT versus physician-selected standard of care for patients with metastatic disease. In addition, they are leveraging the findings from the clinical trial to interrogate and define a set of network models representing major relevant changes in pancreatic cancer cells that associate significantly with response or resistance to standard therapies. This work is expected to culminate in a version 2.0 molecular algorithm for the next, larger clinical trial. The team is also defining novel chemoresistance mechanisms and identifying targets to overcome such resistance in pancreatic cancer cells.

Defining novel combination KRAS-targeted therapeutic strategies
Channing J. Der, PhD
Lead Principal Investigator

Channing J. Der, PhD

Sarah Graham Kenan Distinguished Professor of Pharmacology
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina

Jason B. Fleming, MD
Co-Principal Investigator

Jason B. Fleming, MD

Professor and Chief, Pancreas Surgery
University of Texas MD Anderson Cancer Center
Houston, Texas

Krister Wennerberg, PhD
Co-Principal Investigator

Krister Wennerberg, PhD

FIMM-EMBL Group Leader
Institute for Molecular Medicine Finland, University of Helsinki
Helsinki, Finland

Research
The frequent mutation of the KRAS gene in pancreatic cancer, together with compelling evidence that “correction” of this gene defect can significantly halt pancreatic cancer growth, has made the development of anti-KRAS drugs imperative. The frequent mutational activation of two key KRAS effectors (BRAF and PIK3CA), and their well-validated roles as cancer drivers, has led to extensive ongoing clinical trials evaluating a large roster of inhibitors of these pathways. However, significant hurdles remain, specifically normal tissue toxicity and drug resistance. In this project, unbiased functional screens are being applied to identify combinations that can effectively suppress the RAF-MEK-ERK and PI3K-AKT-mTOR effector pathways. Finally, the best available preclinical models are being applied for prediction of therapies that can be most effective in pancreatic cancer patients.

Eliminating T cell barriers in pancreatic cancer patients
Steven D. Leach, MD
Lead Principal Investigator

Steven D. Leach, MD

Director, Rubenstein Center for Pancreatic Cancer Research
Memorial Sloan Kettering Cancer Center
New York, New York

Douglas T. Fearon, MD
Co-Principal Investigator

Douglas T. Fearon, MD

Walter B. Wriston Professor of Pancreatic Cancer Research
Weill Cornell Medical College
New York, New York

Research
Dr. Fearon’s group previously discovered that pancreatic tumors secrete CXCL12, a protein that effectively eliminates immune cells from the local tumor environment. Blocking CXCL12 sensitizes mouse pancreatic cancers to immune attack, leading to rapid tumor destruction. Drs. Leach and Fearon partnered with Bristol Myers Squibb to initiate preclinical studies of longer-lasting antibodies targeting CXCL12 and its receptor, CXCR4. At the same time, the team’s clinical co-investigators, Eileen O’Reilly, Jedd Wolchok, Manish Shah, and Peter Allen, have launched two additional clinical trials evaluating this antibody-based approach in patients with either localized or metastatic pancreatic cancer. As a critical foundation for these trials, Dr. Leach and co-investigator Tim Chan are charting the neoepitope landscape of pancreatic cancer by determining the quantity and quality of effective T-cell neoepitopes in a series of patients with resected pancreatic cancer.