Dr. Stanley Liu

Sunnybrook Research Institute 

Notch inhibition and radiotherapy as a novel strategy for prostate cancer treatment: elucidating mechanisms of action and resistance

2011-2013

Radiation therapy uses high energy radiation to shrink and kill prostate cancer. Although it is an effective treatment, not all prostate tumours are controlled with radiation. Therefore, Dr. Liu is researching ways to improve the effectiveness of radiation treatment. Previous research on mice that are growing human cancer has shown that by administering a drug called a 'Notch inhibitor' prior to a radiation treatment results in more cancer cells being killed than if the same dose of radiation was given without the drug. This effect is called ‘radiation sensitization’. This research suggests that ‘Notch inhibitors may allow for more effective control of cancers when combined with radiation , with no increased toxicity. This effect appears to happen partly due to changes in the tumour blood vessels which reduce their function, and deprive the tumour of oxygen and nutrients. Dr. Liu will now test this innovative treatment strategy in human prostate cancer to determine if cancer growth can be profoundly delayed. He will also explore the mechanism behind how this treatment is working in prostate cancer, by determining what different ‘angiogenic’ (tumor blood vessel formation) pathways are affected, and also see how the treatment decreases tumour initiating cells, which are believed to be more resistant to standard treatment approaches. Tumours eventually grow back after treatment. Therefore, Dr. Liu will screen for bypass pathways that the tumors may be using, to help identify how these pathways may be blocked, thus making the treatment more effective. This translational research may lead to an optimal treatment, which will ultimately be tested in prostate cancer patients undergoing radiation therapy.

 

Dr. Jehonathan Pinthus

Juravinski Cancer Centre

Personalizing prevention strategies for prostate cancer using hair follicle and salivary glands oxidative stress status as surrogacy

2011-2013

A major cause of prostate cancer development and progression is the accumulation of toxic oxygen radicals, through a process termed oxidative stress. Oxidative stress is influenced by aging, testosterone (the main male androgen/hormone) stimulation, diet and genetics. It has been speculated that prostate cancer can be prevented by reducing oxidative stress through the use of anti-oxidants such as vitamin E, vitamin C, and selenium supplementation or by inhibiting androgen stimulation using a family of drugs named 5-alpha reductase inhibitors (5-ARI). Despite initial enthusiasm, clinical studies have revealed no protective effects for supplementation with anti-oxidants, or 5ARI usage. This may be because only certain men will benefit from these types of interventions.  Thus, methods that can predict the oxidative stress status in the prostate on an individual basis may greatly enhance the identification of men at risk for prostate cancer and consequently improve the effectiveness of prevention interventions such as antioxidants and 5-ARIs. Recent research in rats has shown that there is a close correlation between levels of oxidative stress in the prostate, hair follicles and salivary glands. This correlation offers the ability to easily and non-invasively assess levels of oxidative stress in the prostate. Dr. Pinthus will investigate the feasibility of this approach to predict the development of prostate cancer in mice that are genetically engineered to develop prostate cancer and to assess the response to anti-oxidative stress and hormonal prevention treatments such as 5-ARIs. This research may eventually lead to a novel, personalized approach for the detection and prevention of prostate cancer.