Grant: DRA: Canada Impact+ Research Training Awards - Doctoral

Breast cancer has approximately 52% 5-year survival rate with no available cure at late metastatic stages. The metastatic nature of this cancer is the major risk factor that affects patients' survival and prognosis. Several reports and studies highlighted the rare occurrence of pregnancy-associated breast cancer, indicating a potential molecular anti-tumor mechanism. Recent studies demonstrated that placenta-secreted factors and T-cells, modulate the inflammatory crosstalk between breast tumor and the placenta in pregnancy-associated breast cancer models. We hypothesize that there is a bi-directional cross talk between the breast cancer cells and the placental trophoblasts mediated by the flow of signaling and anti-tumor factors leading to changes in gene expression levels of both cells at different cell cycles. We expect that the inflammatory tumour-microenvironment will negatively impact the placental barrier and function via unconstrained inflammatory mediators such as cytokines. We will therefore develop an integrated breast-on-chip and placenta-on-chip model to investigate the crosstalk between both cells under biomimetic dynamic conditions. We will use this integrated model to study the molecular interaction between breast cancer cells & trophoblasts. Finally, we will assess the alteration of the molecular profile of both cells upon exposure to nanogold therapeutics including gold nanoparticles (AuNPs), shown to have antioxidant properties, using omics approaches (RNAseng and secretomics) for the different stages of the cell cycles. Finally, we will use AuNPs as model particles with anti-oxidative properties and other RNA therapies. This project will lay the groundwork for safe and efficacious therapies for breast cancer during pregnancy.