2008 Pancreatic Cancer Action Network Research Grants
The Pancreatic Cancer Action Network combines its push for increased federal research funding with direct research support of Fellowships/Young Investigator Awards, Career Development Awards, and Pilot Grants for pancreatic cancer research through a peer-reviewed grant system.

Fellowship Award: One-year grant totaling $45,000 that is awarded to a postdoctoral or clinical research fellow at an academic facility, teaching hospital or research institution who is sponsored by a mentor. The intent of the award is to attract young scientists to a career in pancreatic cancer research.

Career Development Award: Two-year grants totaling $100,000 per award that are provided to junior faculty at academic and medical institutions. The intent of these grants is to support and encourage young scientists to establish a career path in the field of pancreatic cancer research.

Pilot Grant: Two-year grants totaling $100,000 per award that support innovative research in pancreatic cancer. This research may be basic, translational, or clinical in nature. Particular consideration is given to projects that are non-duplicative and have the potential for national application.

In 2008, 11 grants were awarded, totaling $1,045,000 in funding. This year’s research portfolio includes one Fellowship, six Career Development Awards, and four Pilot Grants. Collectively, these grants support junior and senior scientists and provide funding for research in diverse fields of inquiry, including: the origin and causes of pancreatic cancer; the biology of the disease, including underlying physiological and biochemical processes; discoveries in detection, staging and diagnosis; and novel therapeutic strategies.

Since introducing the Research Grants Program in 2003, the Pancreatic Cancer Action Network has provided over $3.7 million in funding for research. This includes six Fellowship/Young Investigator Awards, 23 Career Development Awards, and nine Pilot Grants.

Fellowship Award

Samuel Stroum - Pancreatic Cancer Action Network – AACR Fellowship

Ken-Tye Yong, PhD
State University of New York, Buffalo, NY
Engineering Multimodal Targeted Probes for Pancreatic Cancer Detection

As a postdoctoral student, Dr. Yong’s advisors have been very instrumental in inspiring his interest in pancreatic cancer research. His specific interests are to engineer ultrasensitive materials capable of early diagnosis to help improve patient survival.

The funded research focuses on the development of quantum dots (QDs) with enhanced illumination and magnetic features to enable early diagnosis of pancreatic cancer. QDs are luminescent nanoparticles that can serve as probes for imaging. In previous research, Dr. Yong developed QDs that can selectively visualize pancreatic cancerous cells in vitro (laboratory). However, for in vivo (in the body) application, these prototype QDs lack the properties as a diagnostic tool. Building on his previous research, new QDs-based nanoparticles will be developed which integrate multiple imaging abilities combining optical imaging and magnetic resonance imaging (MRI). The integration of these two imaging modalities will be used to develop a novel nanoparticle system to explore detection of human pancreatic cancer in an animal model. The study results are expected to pave the way for the development of novel contrast agents for optical imaging and MRI, thereby enabling early diagnosis of pancreatic cancer.
 

Career Development Awards

Pancreatic Cancer Action Network - AACR Career Development Award

Marie-Christine Daniel, PhD
University of Maryland, Baltimore County, MD
Multifunctional Nanovectors for Pancreatic Cancer Therapy

After losing her mother from a rare cancer, Dr. Daniel chose to devote her research to this field. She was struck by the aggressiveness of pancreatic cancer and its low survival rate, and is interested in contributing to efforts to improve treatment for this disease.

The funded research focuses on nanotechnology as a therapeutic strategy for pancreatic cancer. Nanocarriers are devices with a size comparable to biological entities such as proteins or viruses but are much smaller than cells. Along with other properties, this confers upon them distinct advantages over traditional small molecule approaches. Among others, they increase blood circulation time compared to small drugs; provide protection of active agents against enzymatic or environmental degradation; and allow combination of several different agents. Nanovectors are in general composed of three parts: a core constituent material, a therapeutic and/or imaging payload, and some biological surface modifiers that enable tumor targeting of the nanoparticle dispersion. The objective of this study is to prepare nanoparticles that combine multiple agents and to test the effectiveness of such an entity against transformed pancreatic cell lines. Upon the preferential entry of a nanovector into a cell, a very large quantity of therapeutic agents will be delivered. This targeted combination therapy is predicted to allow for a dramatic enhancement in potency and efficacy in pancreatic cancer treatment along with a decrease of the side effects.
 

Seena Magowitz - Pancreatic Cancer Action Network – AACR Career Development Award

David Dawson, MD, PhD
University of California, Los Angeles, CA
Wnt Signaling in Pancreatic Cancer Progenitor Cells

As a cancer researcher and sub-specialty gastrointestinal pathologist, Dr. Dawson is acutely aware of the aggressive biology of pancreatic cancer and the poor prognosis for most patients with this devastating disease. This awareness has propelled him to pursue research in this area.

Each pancreatic tumor is made up of a mixed population of cells that have varied biological properties. A very small percentage of these cells, referred to as cancer stem cells, appear to be largely, if not solely, responsible for the ability of the tumor to first evolve and then grow in size, resist chemotherapy and spread elsewhere in the body. Dr. Dawson’s research focuses on how these rare pancreatic cancer stem cells differ from the majority of the cells that make up any individual’s pancreatic tumor, and how these differences might be responsible for the development and aggressiveness of pancreatic cancer. Better understanding the biology of these pancreatic cancer stem cells will facilitate the development of new strategies to target them with drugs or by other means, and thus more effectively treat pancreatic cancer.
 

Blum-Kovler - Pancreatic Cancer Action Network – AACR Career Development Award

Joseph Michael Herman, MD
Johns Hopkins University School of Medicine, Baltimore, MD
Evaluation of Focused Radiation to Potentiate a Pancreatic GM-CSF Vaccine

Dr. Herman has devoted his career to pancreatic research in the hope of improving the quality and quantity of life of patients with this diagnosis. He is specifically interested in vaccine therapy because it adds little toxicity to standard treatments. By combining vaccine therapy with radiation and chemotherapy, survival and quality of life can be improved for patients with pancreatic cancer.

The funded research builds on previous work to develop a novel pancreatic vaccine, which is comprised of irradiated (killed) pancreatic cells, that is administered under the skin to induce the body's immune system to attack pancreatic cancer. In patients with resected pancreatic cancer (pancreas tumor surgically removed), a combination of this vaccine with chemotherapy and radiation has been found to improve survival and result in less toxicity than traditional treatments. Vaccine alone may not be adequate for patients with unresectable and metastatic pancreatic cancer because the tumor is bulky and it is hard for the vaccine to penetrate. However, the role of vaccine therapy for these patients has not been sufficiently addressed. The funded research more closely examines this role. Specifically, it uses animal models with pancreatic cancer to test how focused radiation may make the pancreatic vaccine work better and to determine the optimal treatment combination. Single high dose stereotactic (focused) radiation therapy prior to vaccination may be more effective, cause less side effects and be more convenient than standard radiation treatment (which consists of 25 daily treatments). It is hoped that this unique translational mouse model can be used to determine how to optimally combine radiation, vaccine, chemotherapy, and targeted therapy for patients with unresectable, resectable, and metastatic pancreatic cancer.
 

Skip Viragh - Pancreatic Cancer Action Network – AACR Career Development Award

Hyunki Kim, PhD
The University of Alabama at Birmingham, AL
MRI to Monitor Early Pancreatic-Tumor Response to a Novel Triple Therapy

Dr. Kim joined the drug development program for pancreatic cancer treatment at his school after realizing how few drugs were available to treat pancreatic cancer patients. He is inspired to help fill this void and develop new drug treatments.

Investigators in the University of Alabama at Birmingham (UAB) created a new drug named TRA-8, which kills cancer cells without having any bad effects on normal cells. TRA-8 has been very effective in prolonging survival of mice having pancreatic cancer, especially when combined with conventional drugs. Currently, TRA-8 combined with gemcitabine has been tested with a limited number of pancreatic cancer patients at UAB. However, not all patients are expected to respond in the same way to the treatment. The aim of the funded project is to develop a method to determine how each patient responds to these drugs, using magnetic resonance imaging. The results from the imaging method, which will be applied during treatment, will enable treatment plans to be adjusted during therapy, thereby maximizing the therapy efficacy for each individual patient. Plans are to develop the imaging method using an animal model first, and then translate it to human patients. This method will extend and even save many pancreatic cancer patients by minimizing unnecessary treatments.
 

Laurie and Paul MacCaskill - Pancreatic Cancer Action Network – AACR Career Development Award

Lorenzo F. Sempere, PhD
Dartmouth Medical School, Hanover, NH and Dartmouth-Hitchcock Medical Center, Lebanon, NH
Role of MicroRNAs in Initiation and Progression of Pancreatic Cancer

Last year, Dr. Sempere's close relative died of pancreatic cancer within a month following diagnosis. Although she had experienced some minor health issues associated with her diabetes, nothing suggested cancer. Dr. Sempere's research is dedicated to her memory and to the hope that his work may provide new tools for early detection and treatment of this stubborn and aggressive disease.

The funded project will examine the role of microRNAs in pancreatic cancer. microRNAs are a recently discovered class of unusual and very short genes. They do not code for proteins and hence are referred to as noncoding RNAs. microRNAs are thought to regulate key processes that keep the cells at check and prevent them from developing cancer. Recent reports have shown that there are changes in the levels of microRNAs between normal and tumor tissues of patients suffering from different types of cancer, including pancreatic cancer. The funded study will use a special staining technique called in situ hybridization to visualize exactly where changes of selected microRNAs occur in the pancreas of mouse models that have been purposely designed to develop pancreatic cancer. Since pancreatic tissue is composed of different cell types and only some of these cells are susceptible to develop cancer, it will be important to know if these microRNA changes occur within the cancer-prone cells. If so, then, the study will determine whether having too much or too little of a specific microRNA affects the growth and survival properties of the pancreatic cancer cells in vitro and in vivo.
 

Patty Boshell - Pancreatic Cancer Action Network – AACR Career Development Award

Peter Storz, PhD
Mayo Clinic, Jacksonville, FL
Kinases Regulating Pancreatic Cancer Resistance to Chemotherapeutics

Dr. Storz chose to focus his research on pancreatic cancer since he recognized that it is the most aggressive cancer and requires a more aggressive and innovative approach to improve patient outcomes. His specific interest is in discovering new molecular targets for the development of novel drugs that allow better response to chemotherapy and prevent recurrence.

The funded project is designed to identify cellular signaling proteins (kinases) that regulate resistance of pancreatic cancer cells to chemotherapeutic agents. Such kinases may serve as potential drug targets for pancreatic cancer therapy. A global approach will be employed to uncover key enzymes and test if some of them could serve as targets for novel therapeutics to decrease the resistance of pancreatic cancer to chemotherapy drugs. Study results are expected to contribute to the development of a pharmacologic strategy to re-sensitize pancreatic tumor cells to conventional chemotherapeutic drugs, thereby providing new avenues for therapeutic intervention in this disease.
 

Pilot Grants

Randy Pausch, PhD - Pancreatic Cancer Action Network – AACR Pilot Grant

Nabeel Bardeesy, PhD
Massachusetts General Hospital, Boston, MA
Molecular Markers of Drug Sensitivity in Pancreatic Cancer

Dr. Bardeesy’s interest in pancreatic cancer research developed while pursuing his postdoctoral studies and was sparked by a fellow student who had lost two family members to the disease. This experience highlighted the urgency for an improved understanding of the biology of the disease and the need to discover effective treatment options.

The funded project focuses on the development of improved approaches to pancreatic cancer treatment. In other cancers, progress in treatment has come from the observation that some patients respond to certain therapies and that this response is due to specific genetic alterations in the tumor cells. The importance of this discovery is that it demonstrates that different drugs can be matched or “tailored” to patients with these genetic changes who are most likely to benefit from these treatments. Only about 10% of patients with pancreatic ductal adenocarcinoma are responsive to targeted and conventional therapeutics. This study plans to analyze the responsiveness of cells derived from many different pancreatic cancer patients to a large set of anti-cancer drugs and then compare the drug sensitivity with the genetic features of the cancer to determine which features predict drug responsiveness. Predictions will be tested using a series of mouse models that resemble the human disease. Overall, the study is expected to define distinct subgroups of pancreatic ductal adenocarcinoma, provide new insights into cancer therapeutics, and directly inform the design of refined clinical trials.
 

Pancreatic Cancer Action Network – AACR Pilot Grant

Dafna Bar-Sagi, PhD
New York University School of Medicine, New York, NY
Impact of Diet-Induced Hyperlipidemia on Pancreatic Inflammation and Cancer

Dr. Bar-Sagi’s involvement in pancreatic cancer research resulted from her interest in making a difference in understanding and curing a disease for which things have been hopelessly the same for the past few decades.

The funded project focuses on the relationship between high fat diet-induced hyperlipidemia and the development of pancreatic cancer. Hyperlipidemia is an excess of fatty substances called lipids, largely cholesterol and triglycerides, in the blood. High fat diet and obesity have been implicated in the etiology of chronic pancreatitis (inflammation of the pancreas) and pancreatic cancer. However, the mechanistic basis of this association remains unknown. The overall goal of the project is to establish a mouse model and investigate this link. The experimental design will take advantage of mice that have been genetically engineered to develop hyperlipidemia following feeding of a high fat diet. These mice will be employed to (1) characterize the structural changes that the pancreas endures in response to hyperlipidemia, and (2) assess the effects of hyperlipidemia on pancreatic cancer development. By exploring the cause-and-effect relationships between hyperlipidemia and pancreatic carcinogenesis, these studies will provide new insights into the epidemiological connection between obesity, high fat diet and pancreatic cancer.
 

Michael C. Sandler - Pancreatic Cancer Action Network – AACR Pilot Grant

Matthias Hebrok, PhD
University of California, San Francisco, CA
NF-kB Signaling in PanIN Formation

Dr. Hebrok became interested in pancreatic adenocarcinoma when one of his colleagues at UCSF was diagnosed and eventually succumbed to the disease. Witnessing the rapid decline in his colleagues health, he felt that studying basic aspects of this disease with the intent to gather novel information about potential therapeutic targets was an important goal.

The funded project involves genetic experiments that explore the role of NF-kB signaling in the progression of healthy pancreatic epithelium (the cellular covering of the pancreas) to pre-cancerous lesions. Pancreatic ductal adenocarcinoma (PDAC) develops through a sequence of precancerous lesions termed “pancreatic intraepithelial neoplasias” or PanINs. Recently, mouse models of PDAC have been described that repeat in its development human PanIN progression. However, because lesion formation in these mice occurs gradually and the onset of specific stages is variable, the molecular requirements for the different stages have been difficult to interpret. A rapid and synchronized mouse model of PDAC precancerous lesions has been developed using chemical induction of pancreatitis (inflammation of the pancreas), which is frequently correlated with PDAC in humans. The use of this model allows the role of specific pathways to be efficiently determined in the earliest disease stages. Preliminary data using this model show that NF-kB signaling, a pathway that is involved in inflammation and cell proliferation and is highly active in human pancreatitis and PDAC, plays a significant role in lesion formation. This study aims is to better understand the mechanisms by which this pathway guides the progression from normal pancreatic cells to PanINs. Plans are to characterize the effects of disrupting NF-kB signaling in PanIN progression and determine which cells, in the transition from normal to disease state, possess active NF-kB signaling. Results are expected to provide the field with important indications of the therapeutic and diagnostic possibilities involving the NF-kB pathway.
 

Pancreatic Cancer Action Network – AACR Pilot Grant

Bin Liu, PhD
University of California, San Francisco, CA
Internalizing Human Antibodies Targeting Pancreatic Tumor Cells In Situ

Dr. Liu’s interest in pancreatic cancer research, and particularly in developing novel anti-body based diagnostics and therapeutics, was sparked by interactions with his colleagues who are treating patients and studying the origin and development of the disease.

The funded project aims to identify internalizing human antibodies that target pancreatic adenocarcinorma cells in situ in their natural tissue microenvironment. Currently, there are very few human antibodies that target pancreatic tumors and even fewer detect early stage tumors. The study examines the following two key hypotheses: (1) Pancreatic tumors, like other tumors, possess unique cell surface molecules that distinguish tumors from non-neoplastic tissues; and (2) A subset of these tumor cell surface molecules are internalizing, and thus can be exploited for tumor-targeted intracellular payload delivery. The methods and strategies used in this study are based on precise procurement of staged tumor cells by laser capture microdissection to select internalizing human antibodies that target pancreatic cells in situ. These novel antibodies, which are human in sequence, can be used in the future to develop noninvasive imaging-based strategies for early pancreatic tumor detection and targeted therapeutics based on tumor-specific intracellular drug delivery.

For a listing of our past PanCAN Grant recipients, please click here.