Grant: Project Grant

Cancer is a complex continuum of diseases caused by dysregulated expression of the genes controlling cell proliferation and survival. Unfortunately, many genes can be involved, which explains why cancers are so diverse in clinical behaviour and response to treatment. More effective treatments require more knowledge of the defective regulatory pathways in individual cancers and new therapies to regulate these pathways. In practical terms this means that more effective cancer treatments will involve combinations of therapeutic agents and greater understanding of how their targets regulate normal and cancer cell behaviour. In our previous work we have studied the function of an enzyme called FER in the hope that it might represent a potential novel therapeutic target in breast cancer. To test this, we genetically engineered mice to no longer produce functional FER and found that they are overtly healthy, suggesting that humans might also tolerate inhibition of FER without serious toxicity; an important consideration for any therapeutic target. When these FER-deficient mice were bred to a strain of transgenic mice which develop breast cancer, we observed a significant attenuation in tumor development. We also learned that FER-deficient tumor cells have greatly reduced potential to spread from the site of tumor origin to other organs. These exciting result suggests that FER might represent a novel therapeutic target in breast cancer, and potentially other cancers as well. We have learned a great deal about how FER contributes to cancer cell behaviour, including metastasis and sensitivity to specific therapeutic drugs currently used to treat breast and other cancers. We now propose to validate FER as a therapeutic target in breast cancer, begin developing inhibitors of FER suitable for clinical use, and determine which drugs to combine with FER inhibitors to achieve maximum therapeutic effects.