Growth Suppression and Therapy Sensitization of Breast Cancer.
Abstract
The purpose of this project is to provide a rationale and pre-clinical evaluation of p53-based approaches to growth suppression and therapy sensitization of breast cancer. The project addresses combination approaches employing p53, DNA damaging chemotherapeutic agents, and retinoids. The scope of the second year's study was to continue to evaluate drugs to be used in combination with p53, to correlate DNA repair and DNA damage levels with sensitivity to p53, to identify intermediates in the p53- mediated pathway of apoptosis, and to identify a model system to carry into pre-clinical studies. We have shown that p53 sensitizes several breast cancer lines to doxorubicin (adriamycin), commonly used for breast cancer treatment. We have shown that cell lines with decreased DNA repair and increased genomic instability, are more sensitive to p53-mediated apoptosis, further supporting the rationale for the combined use of p53 and DNA repair inhibitors. We have demonstrated a novel mechanism by which retinoids and possibly other differentiating agents may synergize clinically with cisplatin, providing a rationale for their combined use. Finally, we have begun in vitro evaluation of a promising pre-clinical animal model for metastatic breast cancer which will enable us to evaluate the clinical potential of these p53 combination approaches.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1998
- Accession Number
- ADB240218
Entities
People
- Ruth A. Gjerset