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<p>Purpose: This narrative review aims to summarize current evidence on antisense oligonucleotide (ASO)-based strategies targeting oncogenic long non-coding RNAs (lncRNAs) and to evaluate their therapeutic potential in cancer initiation, progression, metastasis, and treatment resistance. Methods: A narrative review of preclinical studies was conducted, focusing on ASO-mediated silencing of cancer-associated lncRNAs, including MALAT1, PVT1, NEAT1, and other emerging lncRNAs, across multiple malignancies such as lung, breast, ovarian, gastrointestinal, and head-and-neck cancers. Advances in ASO chemical design and delivery strategies—including lipid and polymeric nanoparticles, ligand-directed conjugates, peptide-based carriers, and gymnotic uptake—were also examined. Results: Preclinical evidence consistently demonstrates that lncRNA-targeted ASOs effectively suppress tumor growth, invasion, metastasis, and chemoresistance while promoting apoptosis. Improvements in ASO chemical modifications and delivery platforms have significantly enhanced ASO stability, biodistribution, and intracellular uptake, thereby improving therapeutic efficacy across diverse cancer models. Conclusion: Targeting oncogenic lncRNAs using ASO-based approaches represents a promising and rapidly evolving strategy in precision oncology. Although substantial progress has been achieved in ASO design and delivery, further optimization and well-structured clinical trials are required to facilitate the translation of these therapies into routine cancer treatment.</p>

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Antisense oligonucleotides: targeting oncogenic long non-coding RNAs for cancer therapy

  • 期刊论文

  • 发表日期：

    2026年3月14日

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  • Hamed Irandoost,
  • Mahdieh Mondanizadeh,
  • Elahe Irandoost

摘要

Purpose: This narrative review aims to summarize current evidence on antisense oligonucleotide (ASO)-based strategies targeting oncogenic long non-coding RNAs (lncRNAs) and to evaluate their therapeutic potential in cancer initiation, progression, metastasis, and treatment resistance. Methods: A narrative review of preclinical studies was conducted, focusing on ASO-mediated silencing of cancer-associated lncRNAs, including MALAT1, PVT1, NEAT1, and other emerging lncRNAs, across multiple malignancies such as lung, breast, ovarian, gastrointestinal, and head-and-neck cancers. Advances in ASO chemical design and delivery strategies—including lipid and polymeric nanoparticles, ligand-directed conjugates, peptide-based carriers, and gymnotic uptake—were also examined. Results: Preclinical evidence consistently demonstrates that lncRNA-targeted ASOs effectively suppress tumor growth, invasion, metastasis, and chemoresistance while promoting apoptosis. Improvements in ASO chemical modifications and delivery platforms have significantly enhanced ASO stability, biodistribution, and intracellular uptake, thereby improving therapeutic efficacy across diverse cancer models. Conclusion: Targeting oncogenic lncRNAs using ASO-based approaches represents a promising and rapidly evolving strategy in precision oncology. Although substantial progress has been achieved in ASO design and delivery, further optimization and well-structured clinical trials are required to facilitate the translation of these therapies into routine cancer treatment.