New Radiation Therapy Systems: Applications to Human Cancer Treatment and Novel Drug Discovery
Abstract
A significant portion of prostate cancer patients fails standard hormonal therapy and will result in developing locally advanced or metastatic disease. Neither surgery nor radiation therapy (RT) achieves long-term remission for many patients. New therapeutic approaches, in combination with RT, are needed. The initial hypothesis was to determine whether the growth inhibition and apoptosis induction by RT in prostate cancer cells may be synergistically enhanced by DNA-methylation inhibitors (DNMTIs) and histone-deacetylase inhibitors (HDACIs). Furthermore, we wanted to evaluate whether prostate cancer cells may possess a novel signaling pathway involving nitric oxide (NO), cGMP and protein kinase G (PKG), which stimulates expression of Inhibitor of apoptosis Proteins (IAPs). The data acquired provide valuable new information on combining radiation therapy and DNMTIs given the effect of this combination on the DNA repair mechanism(s) that could be exploited not only for the treatment of prostate cancer but also in the therapeutic approach of other cancer know to be susceptible to radiation. We have also elucidated the novel role of the NO/cGMP/PKG signaling pathway in regulating apoptotic susceptibility in prostate cancer cells and other types of cancer cells of epithelial origin, including lung cancer and mesothelioma. This new information will be used to develop new agents inhibiting the NO/cGMP/PKG signaling pathway and overall generating better therapeutic approaches for the treatment of epithelial cancers.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2010
- Accession Number
- ADA545682
Entities
People
- Giuseppe Pizzomo