Molecular Targeting of the P13K/Akt Pathway to Prevent the Development Hormone Resistant Prostate Cancer
Abstract
Recently the PI3K/Akt pathway has been found to be a significant factor in the development and progression of prostate cancer. It is our belief that the PI3K/Akt pathway is the critical pathway that is maintaining survival by blocking apoptosis in the absence of hormonal stimulation. We will use molecular targeting to inhibit the phosphorylation of Akt. Celecoxib is a FDA approved COX-2 inhibitor, however unique to celecoxib is its ability to inhibit the phosphorylation of Akt. This effectively turns off the PI3k/Akt pathway leading to apoptosis. Celecoxib has been shown to induce apoptosis in a number of different malignancies. Unfortunately the IC50 of celecoxib is less than usually clinically obtainable. Therefore, in an attempt to improve upon the Akt activity and decrease the IC50 concentration to clinically obtainable levels, Chin et al. synthesized multiple 2nd and 3rd generation compounds. These newer compounds have significantly lower IC50 and thus therapeutic levels can be obtained clinically. We will use celecoxib and these newer compounds to evaluate the effects of combined PI3K/Akt inhibition and androgen ablation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2010
- Accession Number
- ADA529374
Entities
People
- Jonathan Walker
Organizations
- University of Arizona