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 p16. 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 have currently developed a better model for the action of the drug by screening a number of breast cancer cell lines for metylated p16 and then testing the efficacy of the drug in a nude mouse model. A non-invasive blood test has also been developed for the detection of p16 methylation that will allow us to easily identify patients suitable for a 5-Aza-CdR clinical trial. Clinical protocols to accomplish this goal have been approved. A phase II clinical trial with a second drug, Bryostatin-l, has been opened again, but no patients have yet been accrued.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2001
- Accession Number
- ADA398382
Entities
People
- Robert A. Sclafani
Organizations
- University of Colorado Health