The Bristow lab is interested in translating basic science to the treatment of prostate cancer.
- Prostate Radiobiology & Novel Therapies
- DNA Damage and P53
- Hypoxia, DNA Repair and Carcinogenesis
- Molecular Biomarkers of Radioresponse
To achieve the goals of reducing risk and aggression of prostate cancer, the Bristow lab has multidisciplinary collaborations between OCI-PMH basic scientists, radiation and medical oncologists, urologists, pathologists, geneticists and radiologists within the PMH Prostate Program, as well as with national and international collaborators.
Particular projects of current interest in prostate cancer include:
- Discovering repair pathways in normal, precancerous and cancerous cells by utilizing tissue culture and pre-clinical models.
- Demonstrating that repair mechanism abnormally correlates to poor response in the treatment of prostate cancer using prostate cancer tissue banks.
- Developing new diagnostic markers for increased prostate cancer risk and aggression.
- Increasing the understanding of DNA repair in familial prostate cancer.
- Developing targeted drugs for eventual use in the clinical setting.
- Developing ways to predict and prevent the side effects of radiotherapy and chemotherapy using genetic testing and new drugs.
The new tests and drugs are being developed within the Cellular Core I of the STTARR Innovation Centre (www.starr.com) located at the MaRS complex as part of the Radiation Medicine Program within the Princess Margaret Hospital - University Health Network and University of Toronto.
Details on these and other projects can be found below:
Prostate Radiobiology & Novel Therapies
This project determines important endpoints in cell death following irradiation based on experimental treatments within human prostate cancer cells in vitro and in vivo xenografts, in vivo. Ongoing studies are currently using signal transduction and DNA repair inhibitors to augment tumour cell death as potential new cancer therapies. The thrust of this research is to optimize the therapeutic ratio for drug-radiotherapy combinations as a conduit to clinical trials.
DNA Damage and P53
DNA Damage and P53 The molecular knowledge surrounding mammalian DNA-dsb repair is rapidly being accrued using novel molecular and microscopy technologies. The Li-Fraumeni Syndrome (LFS) and other cancer-prone disorders are variably characterized by defects in genomic stability and cell cycle checkpoint control. Subtle or significant defects in the biochemical rejoining of DNA-dsb breaks were observed in certain LFS strains when compared to normal strains. These DNA-dsb repair defects may offer a partial explanation for the increased rates of carcinogenesis observed within the Li-Fraumeni Syndrome. Our p52 program is studying the role of specific p53 phosphoforms during DNA repair. We are also testing novel p53 inhibitors as new cancer therapies.
Hypoxia, DNA Repair and Carcinogenesis
Hypoxia, DNA Repair and Carcinogenesis DNA studies in our lab using prostate cancer cell lines have shown that formation of Rad51-homologous recombination (HR) complexes can be abnormal in malignant cells. This suggests that defective Rad51-HR complex formation exists in cancer cells. We are currently using this information to see if ablation of abnormal Rad51 protein function in cells using DNA repair inhibitors will lead to radiosensitization and an improved therapeutic ratio. Our hypoxia program is directly testing the role of oxygen in modifying DNA repair and carcinogenesis in prostate and other cancers.
Molecular Biomarkers of Radioresponse
Molecular Biomarkers of Radioresponse This project is investigating biomarkers of radiation response within patient's tissues (banked prior to radiotherapy) and correlated to clinical outcome in Phase II and Phase III clinical trials of dose escalated conformal/IMRT radiotherapy. We are studying novel biomarkers within specimens of normal and tumour protein tissue pre- and post-XRT for use in DNA microarray and proteomic analyses. This type of analysis can be used for biomarker discovery. Our lab is also collaborating with external partners to correlate protein biomarkers and prostate radiotherapy response.
This page was last updated October 6th, 2009 at 4:16pm.