Pre-clinical drug study to assess Trastuzumab-resistance in HER2+ breast cancer.

BackgroundIn 2014, there were 24,400 newly diagnosed women with breast cancer in Canada. Breast cancer is the second leading cause of death amongst Canadian women, with lung cancer leading the way. Despite advances in early detection, diagnosis and treatments, The Canadian Cancer Society estimates 22% of deaths due to breast cancer occur in women between the ages of 30-59, while 12% of deaths due to breast cancer occur in women over the age of 60. It is likely that many of these deaths can be attributed to recurrence, resistance or metastasis of the cancer. Breast cancer recurrence can occur at any time, however it generally happens within the first five years. In order to improve our chances of curing breast cancer, we ask ourselves some questions; why does breast cancer recur despite sophisticated diagnosis and treatments and what new strategies can we develop that would prevent recurrence from happening?Goal of proposal:The goal of this project is to identify new strategies that will block recurrence of HER2+ breast cancer. Previously our research team discovered two novel drug combinations that inhibited the growth of HER2+ breast cancer and inhibited some of the proteins involved in recurrence of HER2+ breast cancer. To expand on this discovery, we will test how these new drugs in combination with a current treatment for HER2+ breast cancer, Herceptin®, work to inhibit tumour growth and recurrence. Clinical cases of HER2+ breast cancer will be evaluated for the presence or absence of proteins that drive recurrence and we will compare these results with those we observe in our pre-clinical. The outcome of our study will lead the way for a Phase I clinical trial designed to target proteins that are involved in driving HER2+ breast cancer recurrence, thereby improving standard treatment of care for breast cancer. Aim#1Pre-clinical trial to evaluate inhibition of mTOR and metabolism in combination with the current standard of care treatment Trastuzumab.Aim#2Evaluate pro-survival PI3K-mTOR and autophagy pathways.