New Combination Therapies for Advanced Prostate Cancer Based on the Radiosensitizing Potential of 5-azacytidine
Abstract
The research covered under this award is designed to further study our original finding that the epigenetic drug 5-azacytidine increases the responsiveness of prostate cancer cells and xenografts to radiation therapy by impairment of DNA double strand break repair. One of the most important goals of the project is to examine the efficacy of a combined regimen of 5-azacytidine, androgen ablation therapy, and radiation for treatment of advanced prostate cancers. We here present our second annual report, in which we demonstrate that combining 5-azacytidine with the two standard of care modalities for prostate cancer (androgen ablation and radiation) results in a temporary but complete control of tumor progression in a mouse model utilizing androgen-independent human-derived prostate cancer xenografts. Importantly, a single administration of the experimental regimen halted tumor progression for a period of a month, whereas tumors treated with radiation alone rapidly progressed during that period. Although tumors eventually resumed progression, the overall l time needed for triplication of the median volume was doubled as compared to the tumors treated with radiation alone. We expect that administration of repeat doses at the time of relapse, will further improve the overall outcome of the treatment, and we intend to further examine this hypothesis. We conclude that our proposed novel combination therapy of 5-azacytidine, androgen ablation, and radiation is indeed markedly more effective than the single modalities. These findings solidify the clinical potential of 5-azacytidine for treatment of advanced prostate cancers. In addition, our findings give further credibility to earlier observations that 5-azacytidine re-sensitizes advanced androgen independent tumors to andogen ablation therapy, thereby significantly expanding the applicability of this type of treatment.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2013
- Accession Number
- ADA579071
Entities
People
- Eric Weterings
Organizations
- University of Arizona