Pancreatic ductal adenocarcinoma is the 4th leading cause of cancer death in the USA and one of the deadliest cancers. Our clinical trials demonstrate that screening individuals with an inherited predisposition to pancreatic cancer is effective at identifying pre-invasive neoplasms that can be cured by surgical resection. Markers are needed to improve the ability of screening to detect pancreatic neoplasia. Although pancreatic imaging can identify most pancreatic cancers and IPMNs, it cannot identify microscopic high-grade pancreatic intraepithelial neoplasias (PanINs). Since resecting high-grade PanIN can be curative, accurate markers detectable in pancreatic fluids are needed to identify these lesions. Advances in our ability to detect low concentrations of mutant DNA are making this feasible. Developing methods to safely collect pure pancreatic fluids would likely improve the diagnostic accuracy of markers of pancreatic neoplasia. In addition to markers for early detection, better markers to identify minimal residual disease, tumor recurrence and tumor responses to therapy would likely permit earlier and more effective therapeutic interventions. Circulating tumor DNA is one such marker. We have developed highly accurate methods for measuring markers of pancreatic neoplasia. Therefore, we propose:
Aim #1 : To evaluate somatic mutations and chromosomal alterations as markers of high-grade pancreatic neoplasia in pancreatic juice in patients undergoing pancreatic screening. Specifically: (a) To evaluate somatic mutations (including p53, KRAS, p16), (b): To characterize the chromosomal alterations of intermediate and high-grade PanINs, and (c): To detect chromosomal rearrangements at low-concentration in pancreatic fluids.
Aim #2 : To evaluate pure pancreatic juice as a source of markers of pancreatic neoplasia: Specifically: a) To design an endoscopic pancreatic juice collection catheter, b): To compare the mutational profiles of pure pancreatic juice with those of pancreatic juice collected In the duodenum.
Aim #3 : To evaluate circulating tumor DNA (ctDNA) as a marker of tumor burden in patients with pancreatic cancer including a): as a measure of minimal residual disease and predictor of early recurrence, and b): as a measure of tumor response to therapy.
In order to manage the risk of pancreatic cancers, it is best to diagnose the disease in the early stage, before it invades and becomes a true cancer. We have devised methods to screen persons at high risk of these cancers and now need to make the diagnostic tests highly sensitive. Similar tests can also be used to help manage patients who developed cancer and have had it surgically removed.
|Hata, Tatsuo; Dal Molin, Marco; Suenaga, Masaya et al. (2016) Cyst Fluid Telomerase Activity Predicts the Histologic Grade of Cystic Neoplasms of the Pancreas. Clin Cancer Res 22:5141-5151|
|Childs, Erica J; Chaffee, Kari G; Gallinger, Steven et al. (2016) Association of Common Susceptibility Variants of Pancreatic Cancer in Higher-Risk Patients: A PACGENE Study. Cancer Epidemiol Biomarkers Prev 25:1185-91|
|Yachida, Shinichi; Wood, Laura D; Suzuki, Masami et al. (2016) Genomic Sequencing Identifies ELF3 as a Driver of Ampullary Carcinoma. Cancer Cell 29:229-40|
|Rucki, Agnieszka A; Foley, Kelly; Zhang, Pingbo et al. (2016) Heterogeneous stromal signaling within the tumor microenvironment controls the metastasis of pancreatic cancer. Cancer Res :|
|Faisal, Farzana; Tsai, Hua-Ling; Blackford, Amanda et al. (2016) Longer Course of Induction Chemotherapy Followed by Chemoradiation Favors Better Survival Outcomes for Patients With Locally Advanced Pancreatic Cancer. Am J Clin Oncol 39:18-26|
|Kumar, Abhijeet; Le, Dung T (2016) Hepatocellular Carcinoma Regression After Cessation of Immunosuppressive Therapy. J Clin Oncol 34:e90-2|
|Poruk, Katherine E; Blackford, Amanda L; Weiss, Matthew J et al. (2016) Circulating Tumor Cells Expressing Markers of Tumor Initiating Cells Predict Poor Survival and Cancer Recurrence in Patients with Pancreatic Ductal Adenocarcinoma. Clin Cancer Res :|
|Masica, David L; Dal Molin, Marco; Wolfgang, Christopher L et al. (2016) A novel approach for selecting combination clinical markers of pathology applied to a large retrospective cohort of surgically resected pancreatic cysts. J Am Med Inform Assoc :|
|Poruk, Katherine E; Valero 3rd, Vicente; Saunders, Tyler et al. (2016) Circulating Tumor Cell Phenotype Predicts Recurrence and Survival in Pancreatic Adenocarcinoma. Ann Surg 264:1073-1081|
|Foley, Kelly; Kim, Victoria; Jaffee, Elizabeth et al. (2016) Current progress in immunotherapy for pancreatic cancer. Cancer Lett 381:244-51|
Showing the most recent 10 out of 795 publications