Our laboratory is dedicated to finding a cure for pancreatic cancer. We perform preclinical trials of novel therapeutics using advanced genetically engineered mouse models of pancreatic cancer. With an average survival of less than six months, Pancreatic Ductal Adenocarcinoma (PDA) is a uniquely lethal disease that is responsible for the deaths of over 35,000 people annually in the US. 90% of patients present with advanced disease and in most cases, the tumors are innately resistant to chemotherapy. There is great need for advances in the treatment of PDA.
The core of our laboratory is based on a preclinical trials infrastructure called the “Mouse Hospital”. This effort seeks to evaluate novel drugs in mice with pancreatic cancer in exactly the manner that clinical trials are run in human patients. Tumors are detected and quantified using advanced small animal imaging technologies such as high resolution ultrasound and optical imaging. Once tumors reach enrollment sizes the mice are randomized into therapeutics trials.The use of Pharmacokinetic and pharmacodynamic analyses, functional imaging, microscopy, biochemistry and molecular biology techniques are employed to assess drug mechanisms and understand how treatments perturb relevant molecular pathways. Successful therapies are ultimately translated into the clinical setting through collaborations with oncologists from the Pancreas Center of Columbia University.
Building from this preclinical core, we have a number of translational efforts designed to understanding the biology of how pancreatic tumors respond to therapeutic intervention. In the event that an agent is successful in altering the progression of pancreatic tumors, we study the mechanisms by which this occurs. In the event that an agent does NOT alter tumor progression, we study the mechanisms of resistance to treatment. We also have research efforts in applying advanced imaging technologies to clinical problems in pancreatic cancer, such as early diagnostics and detecting responses to treatment. Finally, there are basic science efforts focused on understanding the underlying biology of pancreatic cancer as a means of identifying new strategies for treating the disease.
Some of our work has focused on mechanisms of resistance to chemotherapy. Unlike many cancers, most pancreatic tumors exhibit primary (innate) chemoresistance rather than secondary (acquired) chemoresistance. By studying tissue perfusion in KPC mice, we learned that drug delivery is compromised in pancreatic tumors, resulting in insufficient drug levels within tumor tissues. We found that the stromal cells of pancreatic tumors participate in this process and identified a small molecule agent (an inhibitor of the Hedgehog pathway) that depletes stromal cells from the pancreatic tumors in KPC mice. This agent facilitated the delivery of chemotherapy to pancreatic tumors and prolonged the survival of KPC mice. (Science, 2009, 324: 1457-1461). Clinical testing of Hedgehog pathway inhibitors is under way and will determine the success of this approach in humans.
Other work being done in the lab varies between testing novel drugs, metabolism, imaging, BRCA2, systems biology, and stroma/immune interactions in PDAC. Please visit the Olive Lab Research page to find out more about what our lab is working on!
The core of our laboratory is based on a preclinical trials infrastructure called the “Mouse Hospital”. This effort seeks to evaluate novel drugs in mice with pancreatic cancer in exactly the manner that clinical trials are run in human patients. Tumors are detected and quantified using advanced small animal imaging technologies such as high resolution ultrasound and optical imaging. Once tumors reach enrollment sizes the mice are randomized into therapeutics trials.The use of Pharmacokinetic and pharmacodynamic analyses, functional imaging, microscopy, biochemistry and molecular biology techniques are employed to assess drug mechanisms and understand how treatments perturb relevant molecular pathways. Successful therapies are ultimately translated into the clinical setting through collaborations with oncologists from the Pancreas Center of Columbia University.
Building from this preclinical core, we have a number of translational efforts designed to understanding the biology of how pancreatic tumors respond to therapeutic intervention. In the event that an agent is successful in altering the progression of pancreatic tumors, we study the mechanisms by which this occurs. In the event that an agent does NOT alter tumor progression, we study the mechanisms of resistance to treatment. We also have research efforts in applying advanced imaging technologies to clinical problems in pancreatic cancer, such as early diagnostics and detecting responses to treatment. Finally, there are basic science efforts focused on understanding the underlying biology of pancreatic cancer as a means of identifying new strategies for treating the disease.
Some of our work has focused on mechanisms of resistance to chemotherapy. Unlike many cancers, most pancreatic tumors exhibit primary (innate) chemoresistance rather than secondary (acquired) chemoresistance. By studying tissue perfusion in KPC mice, we learned that drug delivery is compromised in pancreatic tumors, resulting in insufficient drug levels within tumor tissues. We found that the stromal cells of pancreatic tumors participate in this process and identified a small molecule agent (an inhibitor of the Hedgehog pathway) that depletes stromal cells from the pancreatic tumors in KPC mice. This agent facilitated the delivery of chemotherapy to pancreatic tumors and prolonged the survival of KPC mice. (Science, 2009, 324: 1457-1461). Clinical testing of Hedgehog pathway inhibitors is under way and will determine the success of this approach in humans.
Other work being done in the lab varies between testing novel drugs, metabolism, imaging, BRCA2, systems biology, and stroma/immune interactions in PDAC. Please visit the Olive Lab Research page to find out more about what our lab is working on!