The Pancreatic Cancer Action Network-AACR Fellowship, in memory of Samuel Stroum supports a postdoctoral or clinical research fellow who is in the first three years of his or her fellowship training to conduct pancreatic cancer research and establish a successful career path in this field. The research proposed for funding may be basic, translational, clinical or epidemiological in nature and must have direct applicability and relevance to pancreatic cancer.
2011 GRANTEE
Cosimo Commisso, Ph.D.Postdoctoral Fellow, New York University School of Medicine, New York, New York
Pancreatic Cancer, Macropinocytosis and Nutrient Internalization
"Pancreatic cancer is the fourth leading cause of cancer deaths in the United States, with a five-year survival rate of only 5 percent and an average survival of less than six months. Given these statistics, there is an urgent need to advance the understanding of pancreatic cancer biology and to use this knowledge to devise new modes of therapeutic intervention. Oncogenic mutations in K-Ras are thought to initiate pancreatic cancer and are nearly universal in pancreatic adenocarcinomas. One of the outcomes of a K-Ras mutation is that cells begin to internalize large volumes of the surrounding fluid; a process called macropinocytosis. The function of this complex process in pancreatic cancer cells remains unexplored, but we postulate that it serves to capture and internalize nutrients that are present in extracellular fluids. In this way, cancer cells may enhance their nutrient supply, providing the fuel necessary for them to divide and grow. The objectives of my research are to understand the functional outcome of this process in pancreatic cancer cells and to determine whether preventing it has any detrimental effects on tumor development. To achieve these goals, I will be using cell-based assays as well as mouse models of pancreatic cancer. Our findings could lead to the identification of a novel targeting strategy - blockade of macropinocytosis for the treatment of pancreatic cancer. I am truly honored to be the recipient of the 2011 Pancreatic Cancer Action Network-AACR Fellowship and I am very grateful to my postdoctoral supervisor, Dr. Dafna Bar-Sagi, for her continuing support and mentorship."
Top of Page
2010 GRANTEE
Vikram Bhattacharjee, Ph.D.Postdoctoral Associate, Fox Chase Cancer Center, Philadelphia, PA
Candidate Gene Validation of Sensitizers of Pancreatic Cancer to Gemcitabine
"Pancreatic cancer is one of the most aggressive cancers to date. At the point of diagnosis, most patients' life expectancies are measured in months. While several chemotherapeutic agents have been used to treat pancreatic cancer, none have been very successful in significantly extending the patient's lifespan. Pancreatic adenocarcinoma, the major form of pancreatic cancer, has several risk factors including chronic pancreatitis, advanced age, smoking, obesity, diabetes and genetic predispositions. Chronic pancreatitis has been thought to promote tumorigenesis ultimately resulting in pancreatic adenocarcinoma. Presently, several classes of drugs (anti-proliferative agents, platanating agents, fluoropyrimidines and taxanes) are used to treat pancreatic cancer, but patient response is very poor when compared to other cancers. So, there is a need to identify novel molecular targets that sensitize pancreatic cancer cells to chemotherapeutic agents.
"Gemcitabine (an inhibitor of DNA replication) is of particular interest in our lab because it remains the drug of choice in the treatment of pancreatic cancer. To our knowledge, we have recently completed the first to use newly developed RNA interference (RNAi) technology to screen the complete genome of pancreatic cancer cells to identify genes that maybe new drug targets that enhance the killing of pancreatic cancer cells to gemcitabine. In this screen, every one of the ~23000 genes in the human genome was ablated individually by RNAi, and those genes that increased killing by gemcitabine were identified.
"We are currently undertaking the functional characterization part of our study. We utilize automated microscopy tools in addition to molecular biological approaches that are established in our lab in order to chronicle in real time how these pancreatic cancer cells are being sensitized to gemcitabine via aberrant mitotic processes, direct induction of apoptosis or other forms of cell death. We have the capacity to observe the cells at every stage of the cell cycle before, during and after the addition of drug. We have established pancreatic cancer cells lines that stably express fluorescent marker proteins that enable us to observe and get a handle on how these cancer cells are surviving drug treatment and how coupling siRNA treatment with chemotherapy sensitizes these cells. We have also identified several novel and uncharacterized genes that sensitize pancreatic cancer cells. In our hybridoma facility, we have the ability to generate specific antibodies to these novel proteins allowing us to elucidate their roles and functions in cells.
"I would like to take this opportunity to thank the AACR and the Pancreatic Cancer Action Network for awarding me this fellowship. I am honored to receive this support and realize the expectations associated with such an award. Under the guidance of my mentors, Dr. Tim Yen and Dr. Steve Cohen, I anticipate characterizing major players in survival pathways that are triggered in pancreatic cancer cells that allow them to be resistant to chemotherapeutic treatments. I am very excited about the direction of my research and am confident that the translation of this work from the lab to the clinic will have a positive impact on the outlook of patients diagnosed with pancreatic cancer in the future."
Top of Page