Growth Suppression and Therapy Sensitization of Breast Cancer
Abstract
The goal 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, including combination approaches in which p53 gene therapy is combined with traditional chemotherapy or with inhibitors of DNA repair. We have observed in vitro that p53 + doxorubicin provided an additive to synergistic suppression of breast cancer cell viability. The scope of the fourth year's work was to extend these observations to in vivo breast cancer models in nude mice. Using a sub-cutaneous model with MDA-MB-435 breast cancer cells, we observed that direct intratumoral injection of p53 adenovirus led to a significant suppression of tumor growth that was enhanced in animals that received doxorubicin in addition. Using the MDA-MB-435 orthotopic nude mouse model for breast cancer metastasis, we observed that systemic administration of Adp53 in combination with doxorubicin led to a significant suppression of lung metastases. Taken together these results suggest that p53 gene therapy in combination with conventional therapy could have broad application for breast cancer treatment. We are presently investigating how DNA repair inhibitors affect p53-mediated apoptosis in breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2000
- Accession Number
- ADB259398
Entities
People
- Ruth A. Gjerset