Role of STAT3 signaling transduction pathways in cancer stem cell-associated chemoresistance.

Chemoresistance resulting from cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) results in inconsistent chemotherapeutic efficacy. The co-existence of CSCs and the EMT allows cancer cells to interconvert between differentiated and stem-like states, a phenomenon known as cellular plasticity. Phosphorylated signal transducer and activator of transcription 3 (pSTAT3) has been increasingly identified as a major contributor to CSCs and the EMT, as evidenced from preclinical studies that reversed chemoresistance through STAT3 pathway inhibition. In this review, we discuss mechanisms that center on STAT3 and its target genes responsible for regulating the EMT. We also highlight the current status of clinical trials using STAT3 pathway inhibitors.