STATe-of-the-art approach: Using oligonucleotide decoys to target the "undruggable"
Head and Neck Neoplasms
STAT3 Transcription Factor
Sen and colleagues have shown for the first time the clinical application of an oligonucleotide decoy targeting the oncogenic transcription factor STAT3 for the treatment of head and neck tumors. Intratumoral injection of decoy effectively reduced the activity of STAT3 as evidenced by a decrease in several of its transcriptional targets. However, its low bioavailability makes them unacceptable for systemic therapy. Cyclization of the STAT3 decoy markedly increased its half-life while preserving specificity and showed significant antitumor activity upon systemic delivery in preclinical models of head and neck cancer. These findings have broad therapeutic implications for the treatment of many malignancies.