Kinases are attractive drug targets as evidenced by the number of recent FDA approvals of kinase inhibitors for cancer therapy. The drugs currently in the clinics are against either overexpressed kinases or mutated kinases that are implicated in the disease. However not all druggable kinases are mutated or overexpressed in many cases their activity altered through post-translational modifications. Others and we have identified elevated levels of phosphorylated IKK? in the tumor samples compared to the normal tissues suggesting that the diseased state of IKK? exists phosphorylated state. IKK? like other kinases is regulated by sequential phosphorylation-dephosphorylation events. The lack of phospho-specific antibodies against the various phosphorylated forms of IKK? makes defining the diseased state a challenging endeavor. In this application we will use a novel technology NanoPro 1000 to address this issue in pancreatic tumors and cell lines. This is an exploratory project as we seek to characterize the various post-translational modifications associated with a disease relevant kinase. Our focus on the specific forms of IKK?, rather than IKK? in general, makes this bother novel and innovative.

Public Health Relevance

Pancreatic cancer has a 5-year survival of ~6% and has not changed in the past 25 years. Studies with tumor specimens indicate the presence of TNF? in the tumor microenvironment in 50% of the samples and elevated levels of phosphorylated IKK in the tumor cells when compared to normal cells. In this application; we will use a novel technology NanoPro 1000 to characterize phosphorylated states of IKK? to define its diseased state in pancreatic tumors and cell lines.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
3R21CA182820-01S1
Application #
8907404
Study Section
Special Emphasis Panel (ZRG1-BMCT-C (01))
Program Officer
Kondapaka, Sudhir B
Project Start
2014-01-01
Project End
2015-12-31
Budget Start
2014-07-01
Budget End
2014-12-31
Support Year
1
Fiscal Year
2014
Total Cost
$30,904
Indirect Cost
$8,071
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