Scientists are highlighting long non-coding RNAs (lncRNAs) as promising targets in the effort to overcome one of cancer treatment’s most persistent challenges: therapeutic resistance. A comprehensive review published in Genes & Diseases examines how these RNA molecules can influence resistance to chemotherapy and radiotherapy and explores their potential for improving treatment outcomes.

Cancer treatments have advanced considerably, but tumors can develop mechanisms that allow malignant cells to survive therapy, contributing to recurrence, metastasis and treatment failure. The review identifies lncRNAs as important regulators of these mechanisms because they can alter gene expression, interact with microRNAs and proteins, and influence chromatin. Their effects extend across processes including apoptosis, autophagy, cell-cycle regulation, epithelial–mesenchymal transition (EMT), DNA repair and drug efflux.

The researchers examine evidence from multiple cancer types, including breast, lung, gastric, liver, cervical, colorectal and nasopharyngeal cancers. Particular attention is given to lncRNAs such as MALAT1, HOTAIR, PVT1, NEAT1 and UCA1, which have been associated with pathways that can help cancer cells withstand treatment. Some lncRNAs promote resistance, while others may increase sensitivity to therapy, demonstrating the complexity of these regulatory molecules.

This growing understanding could create new opportunities for precision cancer medicine. Potential approaches include antisense oligonucleotides, RNA interference using siRNAs, and CRISPR/Cas9 gene editing to inhibit or modify lncRNAs involved in resistance. Advances in lipid nanoparticles, exosomes and other delivery technologies could also help transport RNA-targeting treatments more effectively into cancer cells.

However, substantial barriers remain before lncRNA-targeted therapies can become routine clinical treatments. Researchers must address challenges including tissue-specific delivery, unintended effects on other cellular pathways, tumor heterogeneity and differences in lncRNA expression between patients. Long-term safety and efficacy also require further investigation.
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Genes & Diseases publishes rigorously peer-reviewed and high quality original articles and authoritative reviews that focus on the molecular bases of human diseases. Emphasis is placed on hypothesis-driven, mechanistic studies relevant to pathogenesis and/or experimental therapeutics of human diseases. The journal has worldwide authorship, and a broad scope in basic and translational biomedical research of molecular biology, molecular genetics, and cell biology, including but not limited to cell proliferation and apoptosis, signal transduction, stem cell biology, developmental biology, gene regulation and epigenetics, cancer biology, immunity and infection, neuroscience, disease-specific animal models, gene and cell-based therapies, and regenerative medicine.
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Reference
Ashiq Ali, Urooj Azmat, Aisha Khatoon, Bilal Murtaza, Kaynaat Akbar, Ziyi Ji, Urooj Irshad, Kinza Ishaque, Zhongjing Su, Therapeutic resistance in cancer: lncRNAs as modulators and targets for cancer therapy, Genes & Diseases, Volume 13, Issue 6, 2026, 101990, https://doi.org/10.1016/j.gendis.2025.101990