LAUSR

Simple Summary Despite significant advancement in therapeutic strategies, breast cancers remain the most prevalent type of cancer in terms of incidence and mortality worldwide. Therefore, new alternative therapies have become an urgent clinical need. The present study shows a significantly enhanced cytotoxicity and apoptosis of a treatment with the dual topoisomerase inhibitor P8-D6 compared to standard cytostatics. These effects were visible in various breast cancer cell lines and primary patient cells in 2D monolayer and 3D spheroids. In summary, P8-D6 seems to be a potent chemotherapeutic agent for various breast cancer cell treatments. Abstract Breast cancer constitutes the leading cause of cancer deaths among females. However, numerous shortcomings, including low bioavailability, resistance and significant side effects, are responsible for insufficient treatment. The ultimate goal, therefore, is to improve the success rates and, thus, the range available treatment options for breast cancer. Consequently, the identification, development and evaluation of potential novel drugs such as P8-D6 with seminal antitumor capacities have a high clinical need. P8-D6 effectively induces apoptosis by acting as a dual topoisomerase I/II inhibitor. This study provides an overview of the effectiveness of P8-D6 in breast cancer with both 2D monolayers and 3D spheroids compared to standard therapeutic agents. For this drug effectiveness review, cell lines and ex vivo primary cells were used and cytotoxicity, apoptosis rates and membrane integrity were examined. This study provides evidence for a significant P8-D6-induced increase in apoptosis and cytotoxicity in breast cancer cells compared to the efficacy of standard therapeutic drugs. To sum up, P8-D6 is a fast and powerful inductor of apoptosis and might become a new and suitable therapeutic option for breast cancer in the future.