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Decoy oligonucleotide technology in cancer therapy: molecular mechanisms, challenges, and translational potential
Maryam Mahjoubin-Tehran1, Samaneh Rezaei2, Prashant Kesharwani3,4
1Department of Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Abstract:
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.
Insights
Decoy oligonucleotide technology offers a novel cancer therapy by blocking oncogenic signaling before transcription. Advances in delivery and stability enhance its potential for precise gene regulation and durable cancer control.
Area of Science:
- Molecular Biology
- Cancer Therapeutics
- Gene Regulation
Background:
- Decoy oligonucleotide technology targets transcription factor binding to inhibit oncogenic signaling.
- Key transcription factors (STAT3, NF-κB, Ets-1) drive tumor proliferation, invasion, and metabolic reprogramming.
- Decoy interventions show potent antitumor efficacy in various cancer models.
Purpose of the Study:
- To review the advancements in decoy oligonucleotide technology for cancer therapy.
- To highlight the importance of delivery and stability for therapeutic success.
- To discuss the integration of decoy technology with nanocarriers and biomaterials.
Main Methods:
- Review of in vivo studies on decoy molecule pharmacodynamics, toxicity, and stability.
- Analysis of local and systemic delivery strategies for decoy oligonucleotides.
- Examination of nanocarrier and biomaterial integration for enhanced decoy performance.
Main Results:
- Decoy technology effectively blocks pre-transcriptional oncogenic signaling.
- In vivo studies demonstrate improved understanding of decoy pharmacodynamics and stability.
- Nanocarrier and biomaterial systems enhance decoy stability and tumor selectivity.
Conclusions:
- Decoy oligonucleotides represent a promising molecular strategy for cancer therapy.
- Enhanced delivery and protection are critical for therapeutic efficacy.
- Integration with advanced systems positions decoy technology for precise gene regulation and cancer control.
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