Chemotherapy of Late Stage Breast Cancer Targeted Towards Cell Cycle Regulatory Components
Abstract
Two drugs have been studied as potential therapeutic agents for late stage breast cancer patients. 5-aza-2'deoxycytidine (5-Aza-CdR), is an inhibitor of DNA methylation and is targeted for re- expression of a repressed tumor suppressor gene known as pl6. Re-activation of the p16 gene in cells in which the gene is methylated will restore normal growth control and be efficacious in treatment of breast cancer patients. Both p16 protein expression and de-methylation of the p16 promoter occurs in breast cancer cells, treated with 5-Aza-CdR. 5-Aza-CdR also destroys the ability of the cells to grow in an anchorage-dependent manner, thereby indicating that the drug can inhibit tumorigenesis. We are currently developing a better model for the action of the drug by screening a number of breast cancer cell lines for methylated p16 and then testing the efficacy of the drug in a nude mouse model. A non-invasive blood-test has been developed for the detection of pl6 methylation that will allow us to easily identifypatients suitable for a 5-Aza-CdR clinical trial. Clinical protocols to accomplish this goal have been submitted. A phase II clinical trial with a second drug, Bryostatin- 1, will continue but has been temporarily halted due to administrative problems.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2000
- Accession Number
- ADA386914
Entities
People
- Robert A. Sclafani
Organizations
- University of Colorado Boulder