This application for a Specialized Program of Research Excellence in Pancreatic Cancer focuses on translational studies that address basic and clinical issues of importance to improving the outcome of patients with pancreatic cancer. Specifically, the research projects in this program seek to: 1) develop and test novel therapeutic strategies including chemotherapy, and chemoradiation therapy for patients with early and advanced pancreatic cancer;2) undertake basic research studies in conjunction with clinical trials that will provide insight at the molecular level into the reasons for success and failure of the different strategies. The first project investigates potential of novel inhibitors of CDKS to block tumor progression and nociceptive signaling (pain) in preclinical animal models and in a phase I clinical trial in patients that have failed other therapies. The second project investigate further the molecular nature of radioresistance in patients with borderline resectable disease and proposes a clinical trial with inhibitors of the cholesterol synthesis pathway (Zometa) as a therapeutic intervention. The third project investigates therapeutic strategies that may be effective in SMAD4 mutant and SMAD4 wildtype tumors and proposes a novel clinical trial with a combination of an HDAC inhibitor (Belinostat) and an inhibitor to surviving (YM155) in patients that have failed other therapies. The fourth project investigates the possibility that a hypoxic an desmoplastic environment in pancreatic cancer affects metabolic features of the tumor and stroma that result in high endogenous production of cytidine, which in turn causes drug resistance to fluropyrimidines. Two therapeutic strategies that inhibit hypoxia (digoxin) and pyrimidine biosynthesis (leflunomide) will be investigated in a clinical trial, and the possibility that cytidine and associated metabolites can serve as biomarkers of drug resistance will be investigated. Our tissue core proposes to continue its unique collection of metastatic tumor samples through our rapid autopsy program, in addition to capturing samples associated with surgical resections. All projects are supported by administrative and biostatistics cores.

Public Health Relevance

This application for a Specialized Program of Research Excellence in Gastrointestinal (Pancreatic Cancer) will focus on translational studies that address basic and clinical issues of importance to improving the outcome of patients with pancreatic cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
2P50CA127297-06A1
Application #
8738887
Study Section
Special Emphasis Panel (ZCA1-RPRB-0 (M1))
Program Officer
Agarwal, Rajeev K
Project Start
2008-09-05
Project End
2019-08-31
Budget Start
2014-09-23
Budget End
2015-08-31
Support Year
6
Fiscal Year
2014
Total Cost
$2,162,000
Indirect Cost
$725,455
Name
University of Nebraska Medical Center
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
168559177
City
Omaha
State
NE
Country
United States
Zip Code
68198
Krasnoslobodtsev, Alexey V; Torres, MarĂ­a P; Kaur, Sukhwinder et al. (2015) Nano-immunoassay with improved performance for detection of cancer biomarkers. Nanomedicine 11:167-73
Kaur, Sukhwinder; Sharma, Neil; Krishn, Shiv Ram et al. (2014) MUC4-mediated regulation of acute phase protein lipocalin 2 through HER2/AKT/NF-*B signaling in pancreatic cancer. Clin Cancer Res 20:688-700
Liu, Xiang; Yi, Chunhui; Wen, Yunfei et al. (2014) Interactions between MUC1 and p120 catenin regulate dynamic features of cell adhesion, motility, and metastasis. Cancer Res 74:1609-20
Momi, Navneet; Kaur, Sukhwinder; Rachagani, Satyanarayana et al. (2014) Smoking and microRNA dysregulation: a cancerous combination. Trends Mol Med 20:36-47
Kane, Daniel P; Shcherbakova, Polina V (2014) A common cancer-associated DNA polymerase ? mutation causes an exceptionally strong mutator phenotype, indicating fidelity defects distinct from loss of proofreading. Cancer Res 74:1895-901
Stark, Jaime L; Mehla, Kamiya; Chaika, Nina et al. (2014) Structure and function of human DnaJ homologue subfamily a member 1 (DNAJA1) and its relationship to pancreatic cancer. Biochemistry 53:1360-72
Mehla, Kamiya; Singh, Pankaj K (2014) MUC1: a novel metabolic master regulator. Biochim Biophys Acta 1845:126-35
Mimeault, Murielle; Batra, Surinder K (2014) Molecular biomarkers of cancer stem/progenitor cells associated with progression, metastases, and treatment resistance of aggressive cancers. Cancer Epidemiol Biomarkers Prev 23:234-54
Kaur, Sukhwinder; Momi, Navneet; Chakraborty, Subhankar et al. (2014) Altered expression of transmembrane mucins, MUC1 and MUC4, in bladder cancer: pathological implications in diagnosis. PLoS One 9:e92742
Dey, Parama; Rachagani, Satyanarayana; Vaz, Arokia P et al. (2014) PD2/Paf1 depletion in pancreatic acinar cells promotes acinar-to-ductal metaplasia. Oncotarget 5:4480-91

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