Targeted Delivery of STAT-3 Modulator to Breast Cancer Stem-Like Cells Downregulates a Series of Stemness Genes

Cancer stem cells are known to be controlled by pathways that are dormant in normal adult cells, for example, PTEN, which is a negative regulator of transcription factor STAT3. STAT3 regulates genes that are involved in stem cell self-renewal and thus represents a novel therapeutic target of enormous clinical significance. Studies on breast cancer stem cells (BCSC) have been also significantly correlated with STATs. We describe here for the first time a novel strategy to selectively target CSCs and to induce downregulation of STAT3 downstream target genes reducing expression of series of "stem-ness genes" in treated tumors. In vitro and in vivo experiments were performed to evaluate functional activity with gene and protein expression studies. The results of the study indicate that this targeted delivery approach deactivates STAT3 causing a reduction of CD44⁺/CD24^– CSC populations with aptly tracked gene and protein regulations of "stemness" characteristics. Mol Cancer Ther; 17(1); 119–29. ©2017 AACR.

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