| DEVELOPMENT
OF ONCOLYTIC ADENOVIRUSES FOR TARGETING OF REFRACTORY
PROSTATE CANCERS, ENHANCEMENT OF CYTOTOXICITY BY COMBINATION
THERAPIES.
Dr Gunnel Halldén St Bartholomew's Hospital and the London, Queen Mary's School of Medicine |
 |
Prostate cancer is a major cause of death in men. In early stages, progression can be prevented by hormone-deprivation, cytotoxic drugs and radiation therapies but later almost all cancers develop hormone-independent growth, refractory to hormone-ablation therapies. These late-stage hormone-refractory prostate cancers also become resistant to all current therapies. Therefore, no effective treatment is currently available for this patient group and new therapies are needed.
Adenoviruses can be engineered to specifically target cancer cells while leaving normal cells unharmed and also do not generate treatment resistance cancers. Data from numerous clinical trials are promising, demonstrating no cross-resistance with other therapies and limited toxicity.
This project was aimed at finding novel treatments to improve anti-cancer therapies for late-stage prostate cancers, focusing on replication-selective oncolytic adenoviral mutants. Several oncolytic mutants were constructed and characterized. These mutants had improved potency and could specifically kill cancer cells with low toxicity in normal cells. In addition, our new mutants could further improve cancer cell death in response to commonly used anti-cancer drugs (chemotherapy) such as docetaxel and mitoxantrone. The efficacy of selected mutants was further verified in animal models of prostate cancer demonstrating promising anti-cancer activity. Ongoing work is aimed at clearly identifying the optimal viral mutant to be developed for further testing in future clinical trials for prostate cancer both with and without treatment with chemotherapy.
The overall goal of our research is to improve the treatment options for late-stage prostate cancer patients by developing potent anti-cancer viral mutants that can be evaluated in clinical trials for potential future therapeutic applications. We anticipate that the data generated in this project will greatly contribute to this goal.
Summary final research report dated 04 January 2008
Project 2005/11