Developmental Research Program

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.

For Washington University researchers, an additional developmental research award is offered for disparities research. The purpose of this award is specifically to support new research projects in pancreas cancer prevention, treatment and survivorship that seek to reduce the disproportionate burden of pancreatic cancer among certain populations. One award will be given annually.

Learn How to Apply and Download the Application Forms for the Disparities Developmental Research Program.

 


2018 Awardees

Chen SPOREDelphine L. Chen, MD
Washington University School of Medicine
Project Title:  Imaging PARP Expression in Pancreatic Cancer
Lay Abstract: Poly(ADP-ribose)polymerase (PARP) inhibitors are a promising new class of anticancer drugs. However, identifying the patients who will best respond to these drugs is challenging, especially in light of the side effects associated with PARPi therapy. We have developed a new positron emission tomography (PET) technique to image PARP expression in tumors. The goal of this project is to test whether we can use this new PET technique to identify patients who will best respond to PARP inhibitors and spare patients from side effects of ineffective treatment.

 

 

 

Liu SPOREYongjian Liu, PhD
Washington University School of Medicine
Project Title:  PET Imaging Guided Drug Delivery for Pancreatic Adenocarcinoma Therapy
Lay Abstract:  Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest forms of human cancer and is a rising major health problem in the US. By the year 2020, PDAC is projected to be the second-leading cause of cancer death in the United States. Because of the lack of early diagnosis tools and ineffective drug delivery for treatment, the median survival of patients with advanced-stage disease is less than one year, and the five-year overall mortality rate approaches 100%, demonstrating the urgent need for new therapies to improve treatment outcomes.

A nanoparticle is a microscopic-sized vehicle that improves cancer imaging and drug delivery efficiency. Nanoparticles have been used successfully to improve the treatment outcome of cancer patients, but not in PDAC. In this study, we plan to develop an ultrasmall nanoparticle to enhance chemotherapy drug delivery to pancreatic tumors. To improve the delivery efficiency and treatment accuracy, we propose a targeted mechanism using a peptide binding to a protein called CCR2, which is highly expressed on monocytes/macrophages, which are important components of tumor microenvironment and a barrier for PDAC treatment. Through the incorporation of a radioactive atom of copper-64, we propose that the targeted nanoparticle can serve as a platform to deliver chemotherapy drugs more efficiently to PDAC tumors following the real-time imaging guidance. The results obtained from this pilot study will serve as solid foundation for future translation to treatment therapy.  

Toriola SPORE

 

Adetunji Toriola, MD, PhD, MPH
Washington University School of Medicine
Project Title:  Metformin Use and Pancreatic Cancer Survival in African Americans
Lay Abstract:  Pancreatic cancer is the 4th leading cause of cancer death in the US. African Americans have a higher incidence of pancreatic cancer, present with more advanced stages at diagnosis, and are less likely to receive surgery than any other racial group. Reducing these disparities will involve ascertaining factors that improve clinical outcomes in African Americans. Type II Diabetes Mellitus (DM) is one of the few modifiable factors that impacts pancreatic cancer survival. Notably, African Americans are nearly twice as likely as non-Hispanic Whites to have Type II DM. On the basis of the growing evidence that metformin, an anti-diabetic drug, is associated with better survival in pancreatic cancer patients, metformin has been considered a useful adjunctive therapy for pancreatic cancer. Nevertheless, well-designed prospective studies investigating the associations of metformin use with pancreatic cancer survival in African Americans are lacking. Thus, it is impossible to determine whether African Americans with pancreatic cancer will benefit from any survival advantage conferred by metformin, further exacerbating the disparities. Our proposal will begin to address this gap in current knowledge by investigating the associations of metformin use, including duration of use, with survival and other clinical outcomes in African American pancreatic cancer patients with pre-existing type II DM. 


2017 Awardees

Julie SchwarzJulie 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 FieldsRyan Fields, MD, FACS
Washington University School of Medicine
Project Title: An Autologous Humanized Mouse Model to Evaluate Immune Modulating Therapeutics in Pancreatic Cancer
Lay Abstract: 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 Hezel websiteAram 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.

 

 

 

 

2016 Awardees


 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
Washington University
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.