Our research focuses on the cell of origin and the malignant progression of different types of cancer but in particular on breast and ovarian cancer. My group isolates and characterizes cancer stem cells (CSCs) from these tumors and investigates molecular mechanisms of self-renewal and differentiation as well as invasion and metastasis. The aim is to use cancer stem cells from patient tissue to understand their biology and identify new treatment options targeted at the driver of a given tumor. Therefore, the lab uses molecular and genetic in vitro approaches, cell models and animal transplantation, as well as human tumor material and patients’ data. Triple negative breast cancer represents a highly aggressive subtype of breast cancer with over 2 million new cases each year (data from 2018) and is characterized by a significant higher frequency of visceral as well as central nervous system metastases than the other subtypes. Due to this clinical behavior TNBC shows a poor prognosis profile with significant lower recurrence free and overall survival rates, respectively. Breast cancer stem cells (BCSCs) are hypothesized to play a crucial role for the tumorbiological behavior of TNBC with the high metastatic potential as well as the observed metastatic pattern. We were able to isolate and characterize these cells in vitro and in vivo (Metzger and Stepputtis et al, 2017) showing their unique ability to phenocopy the original patient tumor. We are using these cells to generate more accurate cancer models in vitro (De Lorenzi et al, 2023) to identify and test novel therapeutic options. We investigate resistance to therapy (li et al, 2020) and immune escape (Raute et al, 2023) as well as pathways these cell types depend on for survival (Strietz et al, 2016; Narasimhan et al, 2022; Ferraro et al, 2023). Here we present an overview of our work with focus on challenges but also opportunities with these cellular models.