Grant: Project Grant

Modern approaches to treat oncologic malignancies are not only challenged by the lack of efficient targeted therapies but also by constraints associated with the high costs and time exhaustive procedures to bring new drugs to the market. This is particularly critical for those patients with aggressive, invasive cancer or metastatic disease, as they exhibit poor prognosis and short survival outcomes. This proposal will focus on breast cancer, the most frequently diagnosed cancer in women worldwide. Even though the 5-year survival rate for breast cancer patients is at an all-time high of 90%, it remains the second most common cause of cancer-related death in women, only surpassed by lung cancer. This discrepancy largely stems from the fact that BC is a heterogeneous disease, comprising several molecular subtypes exhibiting very different levels of metastatic capacity, resistance to current therapies and survival outcomes. In particular, triple negative breast cancer patients exhibit poor prognosis, high incidence of metastasis and disease progression rates as well as resistance to current chemotherapy regimens and radiotherapy treatments. Thus, there is a clear medical gap and unmet clinical need for these deadly breast tumors. The Lebrun laboratory has developed a cutting edge "Crisperized Medicine" cancer research program to achieve rationalized and personalized management for cancer patients. The platform has been widely recognized by the scientific community and appraised by the public, as it received the award of the top scientific innovation in Quebec in 2021 (Prix Quebec Sciences 2021). The overarching goal of this proposal is to leverage versatile in vivo CRISPR gene editing approaches with custom FDA-approved drug targets libraries to identify effective combination therapies against TNBC, while offering a large window of opportunity for drug repurposing.