The Pancreatic Cancer Action Network-AACR Fellowships, in memory of Samuel Stroum support 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.
Andrew J. Aguirre, M.D., Ph.D.
Clinical Fellow, Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
Validation of Novel KRAS Synthetic Lethal Targets in Pancreatic Cancer
"Oncogenic KRAS mutation occurs in the majority of pancreatic adenocarcinoma and is a high priority therapeutic target. Unfortunately, attempts to develop clinically effective drugs that target mutant KRAS or its effector pathways have proven challenging. The discovery of KRAS synthetic lethal interactions to determine co-dependent signaling pathways that are essential for cancer cell survival is an important avenue for novel target identification. We have recently performed a large-scale pooled lentiviral shRNA screen to systematically identify genetic vulnerabilities across a large number of cancer cell lines, including numerous pancreatic adenocarcinoma cell lines. We have identified several candidate KRAS synthetic lethal target genes as well as a stringently filtered subset of lineage-specific gene dependencies for pancreatic adenocarcinoma. We are undertaking a comprehensive research program to validate candidate genes using both in vitro tumorigenicity assays and in vivo mouse modeling approaches. Additionally, we will develop tumor penetrating nanoparticles for siRNA delivery to mouse models of pancreatic cancer, with the hope of establishing the translational potential of therapeutic gene silencing in human pancreatic cancer.
"I am honored to receive the Pancreatic Cancer Action Network-AACR Fellowship and grateful for this generous support of my research to identify novel therapeutic opportunities in pancreatic cancer. I am also thankful to my mentor, Dr. William Hahn, and to the hematology-oncology fellowship program at Dana-Farber Cancer Institute and Massachusetts General Hospital for their ongoing support of my career as a physician-scientist."
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