Abstract A067: Salinomycin kills not only circulating epithelial tumor cells (CETCs) but also circulating cancer stem cells (cCSC) and may potentially prevent progression in patients with breast cancer

Abstract

Abstract Background: Recently the hypothesis has been proposed that a more aggressive subpopulation of circulating tumor cells, circulating cancer stem cells, are the source of metastatic spread from the primary tumor. These cells are considered to be responsible for treatment relapse and have therefore become a major target in cancer research. The antibiotic salinomycin isolated from Streptomyces albus is the best established cancer stem cell inhibitor and has been shown to reduce the expression of markers for stemness and spheroid-forming ability. The mechanisms of the anticancer effects remain unclear. In this study, we evaluated the cytotoxic effect of salinomycin on CETCs and tumorspheres cultured from cCSC. Methods: 20 patients with breast cancer in different stages of disease were included. The determination of CETCs and cCSC was performed using Maintrac® method and tumorsphere forming assay, respectively. To evaluate the cytotoxic effect of salinomycin on CETCs and spheroids, they were exposed to different concentrations of salinomycin in short time culture for different periods of time. Results: 79% of patients had detectable CETCs and sphere formation was observed in 74% of breast cancer patients. Interestingly, growth of spheroids was detected also in patients without CETCs. The number of tumorspheres increased significantly with tumor progression, especially with presence of metastasis. Treatment with salinomycin showed an 80% reduction in spheroid formation compared with control. Salinomycin reduced the viability of spheroids in a dose-dependent manner. Salinomycin had a stronger cytotoxic effect on CETCs in nonmetastatic as compared to metastatic patients (median of dead CETCs 85% vs. 34%, p<0.001). Similarly, patients without chemotherapy responded better to salinomycin treatment than patients after several lines of chemotherapy (median of dead CETCs 87%vs.35%, p<0.001). Conclusion: Using a method for cultivation of tumorspheres from peripheral blood of cancer patients and an effective in vitro platform for screening anticancer stem cells drugs was developed. Thus it could be shown that salinomycin targets not only more differentiated circulating cancer cells but also cancer stem cells from peripheral blood. It may evolve as a novel and promising therapeutic strategy for future cancer treatment. Citation Format: Monika Pizon, Dorothea Schott, Ulrich Pachmann, Katharina Pachmann, Norbert Szalus. Salinomycin kills not only circulating epithelial tumor cells (CETCs) but also circulating cancer stem cells (cCSC) and may potentially prevent progression in patients with breast cancer [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A067.