Targeting PCNA Phosphorylation in Breast Cancer
Abstract
PCNA, an essential protein in the DNA synthesome, was shown to be phosphorylated at Y211 by a nuclear form of EGFR. A consequence of this alteration has been highly correlated with a reduced survival rate of breast cancer patients. However, no basic or clinical studies have addressed if these inhibitors down-regulate the nuclear function of this protein. Inhibitors of EGFR have exciting potential in other cancer diseases but have failed to show clinical efficacy as a mono-therapy treatment option for breast cancer patients. In addition, therapy resistance in breast cancer patients who initially responded to the inhibitor of ErbB2 receptor tyrosine kinase Lapatinib is now known. Together, these observations call for more specific markers to stage breast cancer patients for effective use of this class of molecular therapeutics. A focused approach to enhance tyrosine kinase inhibitors by intracellular targeting is novel approach under investigation. A main focus of the proposal is to assess if a specific post-translational modification could be an associated specificity marker for malignant tumors.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2011
- Accession Number
- ADA554228
Entities
People
- Anthony Pedley
- Matthew Bartolowits
- Qingshou Chen
- Vincent J. Davisson
Organizations
- Purdue University