Directors: Lee Ratner, MD, PhD, and David Linehan, MD
The goal of the SPORE in Pancreatic Cancer Developmental Research Program is to recruit and support developmental research projects in pancreatic cancer, for future incorporation as full SPORE projects or as the basis for applications for other major peer-reviewed funding. The types of research projects to be supported include basic research, clinical research, epidemiologic studies, and cancer prevention and control in pancreatic cancer. Projects will expand the scope of translational research and increase the number of investigators committed to pancreatic cancer research.
The Developmental Research Program is responsible for:
- Recruiting research projects that will promote pancreatic cancer research to help define the new treatment directions of pancreatic cancer research.
- Supporting early-stage pancreatic cancer research projects so that they may achieve independent funding through competitive applications including R01, SPORE, foundations and other mechanisms.
This program is open to all of the institutions participating in the SPORE, and any of their collaborators to maximize the number of innovative and high-quality projects. In addition, plans call for development of new projects with other SPOREs. This program, along with the Career Enhancement Program, is consistent with the Siteman Cancer Center's overall commitment to the recruitment of minority and underrepresented investigators. New research projects are solicited and funded through developmental funds.
Two to three developmental projects will be funded each year throughout the life of the SPORE. Requests for Applications for developmental projects in pancreatic cancer research will be requested annually. All developmental project applications will be reviewed by a Research Development Advisory Committee consisting of scientists (representing basic and applied science) with expertise in pancreatic cancer, a biostatistician, a patient advocate and ad hoc members, as necessary (special expertise, no conflict of interest). This committee will make recommendations to the Pancreatic Cancer SPORE Steering Committee, which will make final funding decisions.
Learn How to Apply and Download the Application Forms for the Developmental Research Program.
Julie K. Schwarz, MD, PhD
Washington University School of Medicine
Project Title: Targeting the Tumor Stroma to Improve Neoadjuvant Approaches in Pancreatic Cancer
Lay Abstract: Chemo-radiation strategies currently used for pancreatic cancer are disappointingly effective at generating significant tumor regression. This is likely due to our poor understanding of how these therapies impact of the fibrotic and immunologic components of the unique pancreas cancer stroma. Our goal is to understand how to best integrate stromal disrupting therapies to improve responses to radiation therapy in the neoadjuvant setting and to move these therapies into a new clinical approach aimed at directly impacting pancreatic cancer patients.
Ryan Fields, MD, FACS
Washington University School of Medicine
: An Autologous Humanized Mouse Model to Evaluate Immune Modulating Therapeutics in Pancreatic Cancer
: Progress in the early detection and treatment of cancer requires accurate model systems to further evaluate new, promising discoveries. Small animal, and in particular mouse, model systems are attractive to researchers for numerous reasons, including their ease of use and well-described platforms. Immunotherapy has revolutionized clinical oncology, but lacks pre-clinical models of the human immune system and human cancer to investigate new modalities and limitations/toxicities of treatment regimens. The ability to grow human tumors in immunodeficient mice (so-called patient-derived xenografts, or PDXs) allows researchers to work directly with human cancer tissue in a controlled setting. However, PDX models are limited by their lack of an intact immune system. The broad objective of this proposal is to validate an in vivo model to evaluate human tumors in the context of a complete and intact human immune system in a completely personalized and autologous fashion. Herein, we propose to validate the ability to establish humanized mice from patients with pancreatic cancer.
Aram F. Hezel, MD
University of Rochester
Project Title: Arid1a in Pancreatic Cancer; Transcription Control Therapeutic & Clinical Impact
Lay Abstract: The gene Arid1a is mutated in a significant number of pancreatic cancers. We have created new models and systems to study this gene and the effect of its mutation in this disease. Here we will use these systems to understand how cancers with Arid1a mutations may be specifically treated more effectively.
Scott Gerber, PhD
University of Rochester Medical Center
Project Title: Revisiting Neoadjuvant Therapy for Pancreatic Cancer: Incorporation of New Strategies
Lay Abstract: Pancreatic ductal adenocarcinoma (PDAC) continues to have dismal prognosis with surgical resection offering the only real potential for cure. However, even in patients undergoing surgery, the prognosis remains poor due to a high rate of local recurrence and metastases. Therefore, there is a vital need to develop new therapies that will increase the survival rate of patients with PDAC. To that end, our preclinical research project will examine a novel multimodal approach that will not only facilitate surgical removal of the primary malignancy, but may also stimulate a systemic immune response capable of preventing metastases. This approach will combine both radiotherapy and immunotherapy delivered in a neoadjuvant setting, which is defined as treatment that occurs before surgical excision of the tumor. The immunotherapy arm of this treatment is designed to enhance the efficacy of radiotherapy, resulting in a potent systemic anti-tumor immune response. Ultimately, we hope to demonstrate that this novel approach reduces both local recurrence and metastases in patients with pancreatic cancer.
Christopher Maher, PhD
Project Title: Understanding the Role of IncRNAs in Pancreatic Cancer
Lay Abstract: Currently, our limited understanding of how the original pancreatic tumor spreads throughout the body (also known as metastases) is a critical barrier to improve the current inadequate treatments. Although early-stage pancreatic ductal adenocarcinoma (PDAC) is curable with surgery and adjuvant therapy, metastatic pancreatic cancer is usually lethal. To date, PDAC research has primarily focused on protein-coding genes, thereby missing the emerging class of long non-coding RNAs (lncRNAs), which do not generate proteins. While our understanding of how lncRNAs function to promote metastasis is still in its infancy, initial studies suggest that lncRNAs can function by binding with proteins and guiding them throughout the genome to regulate genes involved in cancer. Therefore, the focus of this proposal is to understand how lncRNAs act as a master regulator by interacting with a protein complex known to promote tumor spread/metastases. To accomplish this, we will perform the first analysis that includes normal, primary and multiple distant metastatic tumors from the same patients to discover lncRNAs altered during metastasis. Next, we will identify which lncRNAs confer metastatic properties in cells through their interaction with a protein complex known to promote aggressive disease. Overall, successful completion of these aims will significantly advance our understanding of lncRNA tumor biology and pancreatic cancer metastasis. A better understanding of how lncRNAs enable primary tumors to invade and metastasize could lead to the development of specific treatments to improve patient outcomes.