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1) basic science studies of how the pancreas forms embryologically, 2) cutting-edge genetic analyses of surgically resected cancers, 3) studies of why pancreatic cancer runs in some families, 4) research into the precursor lesions that give rise to invasive pancreatic cancer, 5) the development of new screening tests for early pancreatic cancer, 6) the development and testing of new therapies including a novel vaccine-based therapy to treat pancreatic cancer, and 7) studies of advanced/metastatic pancreatic cancer.
Basic Science EmbryologyDr. Steven Leach in the Department of Surgery Dr. Leach directs an NIH-funded research program focused on cell differentiation in pancreas, using both mouse and zebrafish model systems. The research focuses on "epithelial" cells of the exocrine pancreas, the part of the pancreas that makes and transports enzymes that help us digest our food. This work is based on the general hypothesis that pancreatic cancer may be initiated by characteristic changes in epithelial differentiation. By elucidating the molecular mechanisms regulating exocrine differentiation in developing pancreas, Dr. Leach's lab has provided important new insights regarding abnormal differentiation events occurring during the formation of pancreatic cancer. His work has demonstrated critical links between early forms of pancreatic cancer and the epithelium of the embryonic pancreas, providing exciting new strategies for disease detection and chemoprevention.Genetic StudiesDr. Scott Kern in the Departments of Oncology and Pathology has made many of the fundamental genetic discoveries in pancreatic cancer research. He discovered the DPC4 pancreatic cancer gene and helped discover the second breast cancer gene (called BRCA2). Today Dr. Kern's efforts have turned to using our knowledge of the genetic changes in pancreatic cancer to develop new gene-specific therapies. In particular, he has shown that pancreatic cancers with mutations in one of the Fanconi's anemia genes (including BRCA2) are particularly sensitive to certain forms of chemotherapy (mitomycin C).Dr. Constance Griffin studies the chromosome changes in pancreatic cancer. She reported a chromosome level (karyotyping) analysis of 62 primary adenocarcinomas of the pancreas in an attempt to identify chromosome abnormalities important in this carcinoma. This is the largest number of primary adenocarcinomas of the pancreas which have been studied. Karyotypes were generally complex (more than 3 abnormalities) including both numerical and structural chromosome abnormalities. Many tumors contained at least one marker (unidentifiable) chromosome. Of particular interest, we found double minute chromosomes (DMs) in six tumors; they were observed in 31% of tumors with abnormal chromosomes. DMs are one of two cytogenetic manifestations of gene amplification, and, to our knowledge, these tumors represent the first primary adenocarcinomas of the pancreas with such evidence of gene amplification. Amplification of specific genes has been shown to correlate with a poor prognosis in a number of solid tumors. These genes provide a growth advantage to the tumor, either through action of growth promoting genes, such as oncogenes, or drug resistance genes. Identification of such genes in pancreas cancer would provide important information about its biology. Family Studies
Dr. Alison Klein in the Departments of Oncology and Pathology heads the National Familial Pancreas Tumor Registry at Johns Hopkins. Over 1,600 families have joined this registry allowing Dr. Klein to study, in great detail, why pancreatic cancer runs in some families. Just as we get our hair color and eye color from our parents, so too do some individuals appear to inherit an increased risk of developing pancreatic cancer. Dr. Klein has developed a program (called PancPRO) which can be used to calculate this increased risk precisely, and she is now actively hunting for the familial pancreatic cancer gene. Her research includes studies of large populations as well as smaller studies of specific families.
Dr. Akhilesh Pandey is in the McKusick-Nathans Institute of Genetic Medicine and Departments of Biological Chemistry and Oncology. Dr. Pandey's research focuses on the use of mass spectrometry to identify biomarkers in pancreatic cancers. This field of research is known as "proteomics." He also uses bioinformatics, large databases and genome annotation approaches to understand better the causes of pancreatic cancer. New TreatmentsDr. Anirban Maitra and Manuel Hidalgo have active research labs focused on using the genetic discoveries made by the Hopkins team to develop better patient treatments. They use a variety of cell culture and animal model systems to test large panels of drugs on large numbers of different pancreatic cancers. Click here for animation describing vaccine in detail.
Dr. Elizabeth Jaffee and Dan Laheru are developing cancer vaccines for the treatment of pancreatic cancer. They have already developed one particular vaccine in the laboratory that recently completed the initial phase I and II testing. The vaccine was found to be very safe, and they have identified a vaccine dose that appears to be associated with immune activation and prolonged disease-free survival. They are preparing more vaccine for the next phase of testing of this potential new therapy. Their goal is to complete a study of 50 to 75 patients over the next 3 years who have undergone surgical resection of their pancreatic cancer, and to demonstrate a statistically significance difference in disease-free and overall survival. They are also planning to initiate a phase I study combining chemotherapy and the vaccine in patients with advanced pancreatic cancer. From immune cells obtained from patients who appear to have responded to the vaccine, Drs. Jaffee and Laheru can now begin to identify the proteins (antigens) expressed by pancreatic cancers that are recognized by the immune system. For example, they have shown that the cancer cell protein "mesothelin" is a strong activator of the immune system. They have been developing newer vaccine approaches that employ specific antigens and that seem to be more potent than our current approach. We hope to test these new vaccine approaches that employ these antigens in patients within the next 5 years. Advanced/Metastatic Disease
Dr. Christine Iacobuzio-Donahue studies pancreatic cancer that has spread beyond the pancreas. In 2003, she created the Gastrointestinal Cancer Rapid Medical Donation Program (GICRMDP) at Johns Hopkins. The participation of a remarkable group of volunteers who consented to a rapid autopsy has allowed Dr. Iacobuzio-Donahue to establish a unique collection of pancreatic cancers that have spread ("metastasized") to organs beyond the pancreas. By comparing these metastatic pancreatic cancers to early non-metastatic pancreatic cancers, dr. Iacobuzio-Donahue hope to understand why some pancreatic cancers behave so aggressively. In so doing she hopes to develop new drugs to specifically target late stage pancreatic cancers.
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