Venetoclax Decreases Cell Clusters in TNBC Cells

Mortality associated with breast cancer (BC) is caused by metastasis. The metastatic process involves dissemination of tumor cells from the primary site to distant organs through the bloodstream. The tumor cells found in the bloodstream are called circulating tumor cells (CTCs). The number of CTCs is a predictor of poor survival in BC patients. CTCs exist as single cells or in clusters and have up to 100 times more metastatic potential, higher cell survival, and more resistance to chemotherapy than single CTCs. Our published studies identified high B-cell lymphoma 2 (Bcl2) expression and downregulation of apoptosis pathways in triple-negative BC tumors associated with CTC clusters. Bcl2 is an oncogene that promotes survival and regulates pro- and anti-apoptotic pathways in cancer. The expression of Bcl2 is a poor prognostic marker in TNBC patients, mainly in the absence of adjuvant therapy. However, the role of Bcl2 in clustering of cells needs further investigation. We aimed to evaluate concentration-dependent effects of the Bcl2 inhibitor, venetoclax, on cellular growth in TNBC cells. A significant decrease in the number of clusters with venetoclax at 30mM was found. Ongoing studies explore the effects of Bcl2 knockdown on cell growth and disruption of cellular clustering in TNBC cells.