Decoy oligonucleotide technology in cancer therapy: molecular mechanisms, challenges, and translational potential.

Decoy oligonucleotide technology has emerged as a promising molecular strategy for cancer therapy by selectively inhibiting transcription factor binding to genomic DNA and thereby blocking oncogenic signalling at the pre-transcriptional level. Transcription factors such as STAT3, NF-κB, and Ets-1 are central regulators of tumor proliferation, invasion, and metabolic reprogramming. Decoy-based interventions have demonstrated potent antitumor efficacy across diverse cancer models, offering a novel route to modulate aberrant gene expression. Recent advances in vivo studies have improved the understanding of the pharmacodynamics, toxicity, and therapeutic stability of decoy molecules. The success of this approach depends critically on enhanced delivery and protection from nuclease degradation. While local administration offers targeted benefits for accessible tissues such as skin, lungs, and eyes, systemic delivery remains essential for treating disseminated malignancies. Integration with nanocarrier and biomaterial-based systems has significantly improved decoy stability and tumor selectivity. Collectively, these innovations position decoy technology as a promising next-generation molecular intervention for precise gene regulation and durable cancer control.