Grant: Operating Grant

Breast cancer affects one woman out of nine in North America. Therapeutic progress has led to a regression in death rate from breast cancer, but drug efficacy remains limited as relapse and progression of the disease taking place eventuallly in a significant fraction of cases. To design more efficient drugs, it is important to fully understand the mechanisms of action of current molecules, a process that paradoxically often takes longer than their implementation in the clinic. In this application, we focus on a class of molecules used for the treatment of a specific type of breast cancer that expresses receptors for the sex hormone estrogen. These so-called full antiestrogens have a higher degree of activity in repressing estrogenic action than molecules currently used in standard treatment, but need improvements to maximize action on tumor cells. While there is currently active research in developing new molecules, their mechanisms of action remain imperfectly understood. Following up on our previous research that has led to the identification of novel mechanisms of action of these molecules involving modifications of the estrogen receptor and modulation of its interaction with regulatory proteins, we will now identify the specific features of these molecules that are responsible for these properties, and recapitulate the chain of events that underlies their therapeutic activity.